umu.sePublications
Change search
Refine search result
1 - 14 of 14
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Berk, John L.
    et al.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Obici, Laura
    Sekijima, Yoshiki
    Zeldenrust, Steven R.
    Yamashita, Taro
    Heneghan, Michael A.
    Gorevic, Peter D.
    Litchy, William J.
    Wiesman, Janice F.
    Nordh, Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Corato, Manuel
    Lozza, Alessandro
    Cortese, Andrea
    Robinson-Papp, Jessica
    Colton, Theodore
    Rybin, Denis V.
    Bisbee, Alice B.
    Ando, Yukio
    Ikeda, Shu-ichi
    Seldin, David C.
    Merlini, Giampaolo
    Skinner, Martha
    Kelly, Jeffery W.
    Dyck, Peter J.
    Repurposing Diflunisal for Familial Amyloid Polyneuropathy: A Randomized Clinical Trial2013In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 310, no 24, p. 2658-2667Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Familial amyloid polyneuropathy, a lethal genetic disease caused by aggregation of variant transthyretin, induces progressive peripheral nerve deficits and disability. Diflunisal, a nonsteroidal anti-inflammatory agent, stabilizes transthyretin tetramers and prevents amyloid fibril formation in vitro. OBJECTIVE To determine the effect of diflunisal on polyneuropathy progression in patients with familial amyloid polyneuropathy. DESIGN, SETTING, AND PARTICIPANTS International randomized, double-blind, placebo-controlled study conducted among 130 patients with familial amyloid polyneuropathy exhibiting clinically detectable peripheral or autonomic neuropathy at amyloid centers in Sweden (Umea), Italy (Pavia), Japan (Matsumoto and Kumamoto), England (London), and the United States (Boston, Massachusetts; New York, New York; and Rochester, Minnesota) from 2006 through 2012. INTERVENTION Participants were randomly assigned to receive diflunisal, 250 mg (n=64), or placebo (n=66) twice daily for 2 years. MAIN OUTCOMES AND MEASURES The primary end point, the difference in polyneuropathy progression between treatments, was measured by the Neuropathy Impairment Score plus 7 nerve tests (NIS+7) which ranges from 0 (no neurological deficits) to 270 points (no detectable peripheral nerve function). Secondary outcomes included a quality-of-life questionnaire (36-Item Short-Form Health Survey [SF-36]) and modified body mass index. Because of attrition, we used likelihood-based modeling and multiple imputation analysis of baseline to 2-year data. RESULTS By multiple imputation, the NIS+7 score increased by 25.0 (95% CI, 18.4-31.6) points in the placebo group and by 8.7 (95% CI, 3.3-14.1) points in the diflunisal group, a difference of 16.3 points (95% CI, 8.1-24.5 points; P < .001). Mean SF-36 physical scores decreased by 4.9 (95% CI, -7.6 to -2.2) points in the placebo group and increased by 1.5 (95% CI, -0.8 to 3.7) points in the diflunisal group (P < .001). Mean SF-36 mental scores declined by 1.1 (95% CI, -4.3 to 2.0) points in the placebo group while increasing by 3.7 (95% CI, 1.0-6.4) points in the diflunisal group (P = .02). By responder analysis, 29.7% of the diflunisal group and 9.4% of the placebo group exhibited neurological stability at 2 years (<2-point increase in NIS+7 score; P = .007). CONCLUSIONS AND RELEVANCE Among patients with familial amyloid polyneuropathy, the use of diflunisal compared with placebo for 2 years reduced the rate of progression of neurological impairment and preserved quality of life. Although longer-term follow-up studies are needed, these findings suggest benefit of this treatment for familial amyloid polyneuropathy.

  • 2. Blomström-Lundqvist, Carina
    et al.
    Gizurarson, Sigfus
    Schwieler, Jonas
    Jensen, Steen M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Heart Centre, Umeå University, Umeå, Sweden.
    Bergfeldt, Lennart
    Kennebäck, Göran
    Rubulis, Aigars
    Malmborg, Helena
    Raatikainen, Pekka
    Lönnerholm, Stefan
    Höglund, Niklas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Heart Centre, Umeå University, Umeå, Sweden.
    Mörtsell, David
    Effect of Catheter Ablation vs Antiarrhythmic Medication on Quality of Life in Patients With Atrial Fibrillation: the CAPTAF Randomized Clinical Trial2019In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 321, no 11, p. 1059-1068Article in journal (Refereed)
    Abstract [en]

    Importance: Quality of life is not a standard primary outcome in ablation trials, even though symptoms drive the indication.

    Objective: To assess quality of life with catheter ablation vs antiarrhythmic medication at 12 months in patients with atrial fibrillation.

    Design, setting, and participants: Randomized clinical trial at 4 university hospitals in Sweden and 1 in Finland of 155 patients aged 30-70 years with more than 6 months of atrial fibrillation and treatment failure with 1 antiarrhythmic drug or beta-blocker, with 4-year follow-up. Study dateswere July 2008-September 2017. Major exclusionswere ejection fraction <35%, left atrial diameter > 60 mm, ventricular pacing dependency, and previous ablation.

    Interventions: Pulmonary vein isolation ablation (n= 79) or previously untested antiarrhythmic drugs (n= 76).

    Main outcomes and measurement: Primary outcomewas the General Health subscale score (Medical Outcomes Study 36-Item Short-Form Health Survey) at baseline and 12 months, assessed unblinded (range, 0 [worst] to 100 [best]). There were 26 secondary outcomes, including atrial fibrillation burden (% of time) from baseline to 12 months, measured by implantable cardiac monitors. The first 3 months were excluded from rhythm analysis.

    Results: Among 155 randomized patients (mean age, 56.1 years; 22.6% women), 97% completed the trial. Of 79 patients randomized to receive ablation, 75 underwent ablation, including 2 who crossed over to medication and 14 who underwent repeated ablation procedures. Of 76 patients randomized to receive antiarrhythmic medication, 74 received it, including 8 who crossed over to ablation and 43 for whom the first drug used failed. General Health score increased from 61.8 to 73.9 points in the ablation group vs 62.7 to 65.4 points in the medication group (between-group difference, 8.9 points; 95% CI, 3.1-14.7; P=.003). Of 26 secondary end points, 5 were analyzed; 2 were null and 2 were statistically significant, including decrease in atrial fibrillation burden (from 24.9% to 5.5% in the ablation group vs 23.3% to 11.5% in the medication group; difference -6.8%[95% CI, -12.9% to -0.7%]; P=.03). Of the Health Survey subscales, 5 of 7 improved significantly. Most common adverse events were urosepsis (5.1%) in the ablation group and atrial tachycardia (3.9%) in the medication group.

    Conclusions and relevance: Among patients with symptomatic atrial fibrillation despite use of antiarrhythmic medication, the improvement in quality of life at 12 months was greater for those treated with catheter ablation compared with antiarrhythmic medication. Although the study was limited by absence of blinding, catheter ablation may offer an advantage for quality of life.

  • 3. de Jong, Joop TVM
    et al.
    Komproe, Ivan H
    van Ommeren, M
    el Masri, M
    Araya, Mesfin
    Umeå University, Faculty of Medicine, Clinical Sciences.
    Khaled, N
    van de Put, W
    Somasundaram, D
    Lifetime events and posttraumatic stress disorder in 4 postconflict settings2001In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 286, no 5, p. 555-562Article in journal (Refereed)
  • 4. Di Angelantonio, Emanuele
    et al.
    Gao, Pei
    Khan, Hassan
    Butterworth, Adam S.
    Wormser, David
    Kaptoge, Stephen
    Seshasai, Sreenivasa Rao Kondapally
    Thompson, Alex
    Sarwar, Nadeem
    Willeit, Peter
    Ridker, Paul M.
    Barr, Elizabeth L. M.
    Khaw, Kay-Tee
    Psaty, Bruce M.
    Brenner, Hermann
    Balkau, Beverley
    Dekker, Jacqueline M.
    Lawlor, Debbie A.
    Daimon, Makoto
    Willeit, Johann
    Njolstad, Inger
    Nissinen, Aulikki
    Brunner, Eric J.
    Kuller, Lewis H.
    Price, Jackie F.
    Sundstrom, Johan
    Knuiman, Matthew W.
    Feskens, Edith J. M.
    Verschuren, W. M. M.
    Wald, Nicholas
    Bakker, Stephan J. L.
    Whincup, Peter H.
    Ford, Ian
    Goldbourt, Uri
    Gomez-de-la-Camara, Agustin
    Gallacher, John
    Simons, Leon A.
    Rosengren, Annika
    Sutherland, Susan E.
    Bjorkelund, Cecilia
    Blazer, Dan G.
    Wassertheil-Smoller, Sylvia
    Onat, Altan
    Ibanez, Alejandro Marin
    Casiglia, Edoardo
    Jukema, J. Wouter
    Simpson, Lara M.
    Giampaoli, Simona
    Nordestgaard, Borge G.
    Selmer, Randi
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Kauhanen, Jussi
    Salonen, Jukka T.
    Dankner, Rachel
    Barrett-Connor, Elizabeth
    Kavousi, Maryam
    Gudnason, Vilmundur
    Evans, Denis
    Wallace, Robert B.
    Cushman, Mary
    D'Agostino, Ralph B., Sr.
    Umans, Jason G.
    Kiyohara, Yutaka
    Nakagawa, Hidaeki
    Sato, Shinichi
    Gillum, Richard F.
    Folsom, Aaron R.
    van der Schouw, Yvonne T.
    Moons, Karel G.
    Griffin, Simon J.
    Sattar, Naveed
    Wareham, Nicholas J.
    Selvin, Elizabeth
    Thompson, Simon G.
    Danesh, John
    Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease2014In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 311, no 12, p. 1225-1233Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA(1c)) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA(1c) values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS Analysis of individual-participant data available from 73 prospective studies involving 294 998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (>= 7.5%) risk. RESULTS During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20 840 incident fatal and nonfatal CVD outcomes (13 237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA(1c) values and CVD risk. The association between HbA(1c) values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA(1c) was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA(1c) assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes, additional assessment of HbA(1c) values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

  • 5. Fellman, Vineta
    et al.
    Hellström-Westas, Lena
    Norman, Mikael
    Westgren, Magnus
    Källén, Karin
    Lagercrantz, Hugo
    Marsál, Karel
    Serenius, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Wennergren, Margareta
    One-year survival of extremely preterm infants after active perinatal care in Sweden2009In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 301, no 21, p. 2225-2233Article in journal (Refereed)
    Abstract [en]

    Context Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.

    Objective To determine the 1-year survival in all infants born before 27 gestational weeks in Sweden during 2004-2007.

    Design, Setting, and Patients Population-based prospective observational study of extremely preterm infants (707 live-born and 304 stillbirths) born to 887 mothers in 904 deliveries (102 multiple births) in all obstetric and neonatal units in Sweden from April 1, 2004, to March 31, 2007.

    Main Outcome Measures Infant survival to 365 days and survival without major neonatal morbidity (intraventricular hemorrhage grade >2, retinopathy of prematurity stage >2, periventricular leukomalacia, necrotizing enterocolitis, severe bronchopulmonary dysplasia). Associations between perinatal interventions and survival.

    Results The incidence of extreme prematurity was 3.3 per 1000 infants. Overall perinatal mortality was 45% (from 93% at 22 weeks to 24% at 26 weeks), with 30% stillbirths, including 6.5% intrapartum deaths. Of live-born infants, 91% were admitted to neonatal intensive care and 70% survived to 1 year of age (95% confidence interval [CI], 67%-73%). The Kaplan-Meier survival estimates for 22, 23, 24, 25, and 26 weeks were 9.8% (95% CI, 4%-23%), 53% (95% CI, 44%-63%), 67% (95% CI, 59%-75%), 82% (95% CI, 76%-87%), and 85% (95% CI, 81%-90%), respectively. Lower risk of infant death was associated with tocolytic treatment (adjusted for gestational age odds ratio [OR], 0.43; 95% CI, 0.36-0.52), antenatal corticosteroids (OR, 0.44; 95% CI, 0.24-0.81), surfactant treatment within 2 hours after birth (OR, 0.47; 95% CI, 0.32-0.71), and birth at a level III hospital (OR, 0.49; 95% CI, 0.32-0.75). Among 1-year survivors, 45% had no major neonatal morbidity.

    Conclusion During 2004 to 2007, 1-year survival of infants born alive at 22 to 26 weeks of gestation in Sweden was 70% and ranged from 9.8% at 22 weeks to 85% at 26 weeks.

  • 6. Holme, Oyvind
    et al.
    Loberg, Magnus
    Kalager, Mette
    Bretthauer, Michael
    Hernan, Miguel A.
    Aas, Eline
    Eide, Tor J.
    Skovlund, Eva
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Tveit, Kjell Magne
    Hoff, Geir
    Effect of Flexible Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality A Randomized Clinical Trial2014In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 312, no 6, p. 606-615Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE

    Colorectal cancer is a major health burden. Screening is recommended in many countries. OBJECTIVE To estimate the effectiveness of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality in a population-based trial. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 100 210 individuals aged 50 to 64 years, identified from the population of Oslo city and Telemark County, Norway. Screening was performed in 1999-2000 (55-64-year age group) and in 2001 (50-54-year age group), with follow-up ending December 31, 2011. Of those selected, 1415 were excluded due to prior colorectal cancer, emigration, or death, and 3 could not be traced in the population registry.

    INTERVENTIONS

    Participants randomized to the screening group were invited to undergo screening. Within the screening group, participants were randomized 1: 1 to receive once-only flexible sigmoidoscopy or combination of once-only flexible sigmoidoscopy and fecal occult blood testing (FOBT). Participants with positive screening test results (cancer, adenoma, polyp >= 10 mm, or positive FOBT) were offered colonoscopy. The control group received no intervention.

    MAIN OUTCOMES AND MEASURES

    Colorectal cancer incidence and mortality.

    RESULTS

    A total of 98 792 participants were included in the intention-to-screen analyses, of whom 78 220 comprised the control group and 20 572 comprised the screening group (10 283 randomized to receive a flexible sigmoidoscopy and 10 289 to receive flexible sigmoidoscopy and FOBT). Adherence with screening was 63%. After a median of 10.9 years, 71 participants died of colorectal cancer in the screening group vs 330 in the control group (31.4 vs 43.1 deaths per 100 000 person-years; absolute rate difference, 11.7 [95% CI, 3.0-20.4]; hazard ratio [HR], 0.73 [95% CI, 0.56-0.94]). Colorectal cancer was diagnosed in 253 participants in the screening group vs 1086 in the control group (112.6 vs 141.0 cases per 100 000 person-years; absolute rate difference, 28.4 [95% CI, 12.1-44.7]; HR, 0.80 [95% CI, 0.70-0.92]). Colorectal cancer incidence was reduced in both the 50-to 54-year age group (HR, 0.68; 95% CI, 0.49-0.94) and the 55-to 64-year age group (HR, 0.83; 95% CI, 0.71-0.96). There was no difference between the flexible sigmoidoscopy only vs the flexible sigmoidoscopy and FOBT screening groups.

    CONCLUSIONS AND RELEVANCE

    In Norway, once-only flexible sigmoidoscopy screening or flexible sigmoidoscopy and FOBT reduced colorectal cancer incidence and mortality on a population level compared with no screening. Screening was effective both in the 50-to 54-year and the 55-to 64-year age groups.

  • 7. Holmqvist, Marie E.
    et al.
    Neovius, Martin
    Eriksson, Jonas
    Mantel, Angla
    Wållberg-Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Jacobsson, Lennart T. H.
    Askling, Johan
    Risk of Venous Thromboembolism in Patients With Rheumatoid Arthritis and Association With Disease Duration and Hospitalization2012In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 308, no 13, p. 1350-1356Article in journal (Refereed)
    Abstract [en]

    Context Recent reports suggest that rheumatoid arthritis (RA) may be a risk factor for venous thromboembolism (VTE), particularly in conjunction with hospitalization. Using hospitalization data to identify RA and VTE may identify patients when they are at elevated risk for other reasons, obscuring the incompletely understood underlying association between RA and VTE and leading to inappropriate institution or timing of interventions. Objective To estimate risks for VTE in patients with RA, including the relation of these risks to disease duration and hospitalization. Design, Setting, and Patients Prospective, population-based cohort study of 1 prevalent RA cohort (n = 37 856), 1 incident RA cohort (n = 7904), and matched general population comparison cohorts, all from Sweden, with follow-up from 1997 through 2010. Main Outcome Measure First-time VTE. Results Patients with prevalent RA were at greater risk of VTE than the general population (rate, 5.9 [95% CI, 5.1-6.6] vs 2.8 [95% CI, 2.6-3.1] per 1000 person-years (adjusted hazard ratio [HR], 2.0 [95% CI, 1.9-2.2]; P < .001). By the time of RA symptom onset, there was no statistically significant association between a history of VTE and RA (odds ratio, 1.2 [95% CI, 1.0-1.4]; P = .08; 150 events in the RA cohort vs 587 in the comparison cohort). Counting from RA diagnosis, an increased rate in the RA cohort vs the comparison cohort (3.8 [95% CI, 2.5-5.2] vs 2.4 [95% CI, 1.9-2.9] per 1000 person-years; HR, 1.6 [95% CI, 1.1-2.5]; P = .02) was detected within the first year and did not increase further during the first decade. Although rates for VTE following hospitalization were higher, the 1-year rate of VTE per 1000 person-years was not higher in the RA cohort than in the comparison cohort after hospital discharge (11.8 [95% CI, 8.6-15.1] vs 13.1 [11.3-14.8]; HR, 1.0 [95% CI, 0.7-1.4]; P = .90). The rates of VTE increased with age but were largely similar across sex and rheumatoid factor status, as were the HRs for VTE across age, sex, and rheumatoid factor status. Conclusions Compared with the general population, Swedish patients with RA had an elevated risk for VTE that was stable over the first 10 years after diagnosis. Although hospitalization was a risk factor for VTE the first year after discharge, the excess risk was not greater in patients with RA than in the general population. 

  • 8. Johansson, Mattias
    et al.
    Relton, Caroline
    Ueland, Per Magne
    Vollset, Stein Emil
    Midttun, Øivind
    Nygård, Ottar
    Slimani, Nadia
    Boffetta, Paolo
    Jenab, Mazda
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Kaaks, Rudolf
    Rohrmann, Sabine
    Boeing, Heiner
    Weikert, Cornelia
    Bueno-de-Mesquita, H Bas
    Ros, Martine M
    van Gils, Carla H
    Peeters, Petra H M
    Agudo, Antonio
    Barricarte, Aurelio
    Navarro, Carmen
    Rodríguez, Laudina
    Sánchez, Maria-José
    Larrañaga, Nerea
    Khaw, Kay-Tee
    Wareham, Nick
    Allen, Naomi E
    Crowe, Francesca
    Gallo, Valentina
    Norat, Teresa
    Krogh, Vittorio
    Masala, Giovanna
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Riboli, Elio
    Vineis, Paolo
    Brennan, Paul
    Serum B vitamin levels and risk of lung cancer2010In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 303, no 23, p. 2377-2385Article in journal (Refereed)
    Abstract [en]

    CONTEXT: B vitamins and factors related to 1-carbon metabolism help to maintain DNA integrity and regulate gene expression and may affect cancer risk. OBJECTIVE: To investigate if 1-carbon metabolism factors are associated with onset of lung cancer. DESIGN, SETTING, AND PARTICIPANTS: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 519,978 participants from 10 countries between 1992 and 2000, of whom 385,747 donated blood. By 2006, 899 lung cancer cases were identified and 1770 control participants were individually matched by country, sex, date of birth, and date of blood collection. Serum levels were measured for 6 factors of 1-carbon metabolism and cotinine. MAIN OUTCOME MEASURE: Odds ratios (ORs) of lung cancer by serum levels of 4 B vitamins (B(2), B(6), folate [B(9)], and B(12)), methionine, and homocysteine. RESULTS: Within the entire EPIC cohort, the age-standardized incidence rates of lung cancer (standardized to the world population, aged 35-79 years) were 6.6, 44.9, and 156.1 per 100,000 person-years among never, former, and current smokers for men, respectively. The corresponding incidence rates for women were 7.1, 23.9, and 100.9 per 100,000 person-years, respectively. After accounting for smoking, a lower risk for lung cancer was seen for elevated serum levels of B(6) (fourth vs first quartile OR, 0.44; 95% confidence interval [CI], 0.33-0.60; P for trend <.000001), as well as for serum methionine (fourth vs first quartile OR, 0.52; 95% CI, 0.39-0.69; P for trend <.000001). Similar and consistent decreases in risk were observed in never, former, and current smokers, indicating that results were not due to confounding by smoking. The magnitude of risk was also constant with increasing length of follow-up, indicating that the associations were not explained by preclinical disease. A lower risk was also seen for serum folate (fourth vs first quartile OR, 0.68; 95% CI, 0.51-0.90; P for trend = .001), although this was apparent only for former and current smokers. When participants were classified by median levels of serum methionine and B(6), having above-median levels of both was associated with a lower lung cancer risk overall (OR, 0.41; 95% CI, 0.31-0.54), as well as separately among never (OR, 0.36; 95% CI, 0.18-0.72), former (OR, 0.51; 95% CI, 0.34-0.76), and current smokers (OR, 0.42; 95% CI, 0.27-0.65). CONCLUSION: Serum levels of vitamin B(6) and methionine were inversely associated with risk of lung cancer.

  • 9. Loeb, Stacy
    et al.
    Folkvaljon, Yasin
    Lambe, Mats
    Robinson, David
    Department of Surgery and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden .
    Garmo, Hans
    Ingvar, Christian
    Stattin, Pär
    Department of Surgery and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden .
    Use of Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction and Risk of Malignant Melanoma2015In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 313, no 24, p. 2449-2455Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: The target for the oral erectile dysfunction drugs, phosphodiesterase type 5 (PDE5) inhibitors, is part of a pathway implicated in the development of malignant melanoma. An increased risk of melanoma in sildenafil users was recently reported. OBJECTIVE To examine the association between use of PDE5 inhibitors and melanoma risk, including data on specific PDE5 inhibitors, number of prescriptions, and melanoma stage.

    DESIGN, SETTING, AND PARTICIPANTS: Nationwide, population-based, nested case-control study in the Swedish Prescribed Drug Register, the Swedish Melanoma Register, and other health care registers and demographic databases in Sweden, including 4065 melanoma cases diagnosed from 2006 through 2012 and 5 randomly selected controls per case with matching year of birth.

    EXPOSURES: Number of filled prescriptions for the PDE5 inhibitors sildenafil and vardenafil or tadalafil.

    MAIN OUTCOMES AND MEASURES: Risk of melanoma; overall and by stage and risk of basal cell carcinoma in multivariable logistic regression analyses.

    RESULTS: Of 4065 melanoma cases, 435 men (11%) had filled prescriptions for PDE5 inhibitors, as did 1713 men of 20 325 controls (8%). In multivariable analysis, there was an increased risk of melanoma in men taking PDE5 inhibitors (OR, 1.21 [95% CI, 1.08-1.36]). The most pronounced increase in risk was observed in men who had filled a single prescription (OR, 1.32 [95% CI, 1.10-1.59]; exposure rate, 4% for cases vs 3% for controls), but was not significant among men with multiple filled prescriptions (for 2-5 prescriptions: OR, 1.14 [95% CI, 0.95-1.37], 4% for cases and 3% for controls; for >= 6 prescriptions: OR, 1.17 [95% CI, 0.95-1.44], 3% for cases vs 2% for controls). PDE5 inhibitors were significantly associated with melanoma stage 0 (OR, 1.49 [95% CI, 1.22-1.83], 13% for cases vs 8% for controls) and stage I (OR, 1.21 [95% CI, 1.02-1.43], 12% for cases vs 10% for controls), but not stage II through IV (OR, 0.83 [95% CI, 0.63-1.09], 6% for cases vs 7% for controls). The risk estimates were similar for sildenafil and vardenafil or tadalafil. PDE5 inhibitor use was also associated with an increased risk of basal cell carcinoma (OR, 1.19 [95% CI, 1.14-1.25], 9% for cases vs 8% for controls). Men taking PDE5 inhibitors had a higher educational level and annual income, factors that were also significantly associated with melanoma risk.

    CONCLUSIONS AND RELEVANCE: In a Swedish cohort of men, the use of PDE5 inhibitors was associated with a modest but statistically significant increased risk of malignant melanoma. However, the pattern of association (eg, the lack of association with multiple filled prescriptions) raises questions about whether this association is causal.

  • 10. Lotta, Luca A.
    et al.
    Sharp, Stephen J.
    Burgess, Stephen
    Perry, John R. B.
    Stewart, Isobel D.
    Willems, Sara M.
    Luan, Jian'an
    Ardanaz, Eva
    Arriola, Larraitz
    Balkau, Beverley
    Boeing, Heiner
    Deloukas, Panos
    Forouhi, Nita G.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Skane University Hospital, Malmö, Sweden.
    Grioni, Sara
    Kaaks, Rudolf
    Key, Timothy J.
    Navarro, Carmen
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, Jose-Ramon
    Riboli, Elio
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sacerdote, Carlotta
    Salamanca-Fernandez, Elena
    Slimani, Nadia
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne L.
    van der Schouw, Yvonne T.
    McCarthy, Mark I.
    Barroso, Ines
    O'Rahilly, Stephen
    Savage, David B.
    Sattar, Naveed
    Langenberg, Claudia
    Scott, Robert A.
    Wareham, Nicholas J.
    Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants and Risk of Type 2 Diabetes A Meta-analysis2016In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 316, no 13, p. 1383-1391Article in journal (Refereed)
    Abstract [en]

    Importance  Low-density lipoprotein cholesterol (LDL-C)–lowering alleles in or near NPC1L1 or HMGCR, encoding the respective molecular targets of ezetimibe and statins, have previously been used as proxies to study the efficacy of these lipid-lowering drugs. Alleles near HMGCR are associated with a higher risk of type 2 diabetes, similar to the increased incidence of new-onset diabetes associated with statin treatment in randomized clinical trials. It is unknown whether alleles near NPC1L1 are associated with the risk of type 2 diabetes.

    Objective  To investigate whether LDL-C-lowering alleles in or near NPC1L1 and other genes encoding current or prospective molecular targets of lipid-lowering therapy (ie, HMGCR, PCSK9, ABCG5/G8, LDLR) are associated with the risk of type 2 diabetes.

    Design, Setting, and Participants  The associations with type 2 diabetes and coronary artery disease of LDL-C-lowering genetic variants were investigated in meta-analyses of genetic association studies. Meta-analyses included 50 775 individuals with type 2 diabetes and 270 269 controls and 60 801 individuals with coronary artery disease and 123 504 controls. Data collection took place in Europe and the United States between 1991 and 2016.

    Exposures  Low-density lipoprotein cholesterol–lowering alleles in or near NPC1L1, HMGCR, PCSK9, ABCG5/G8, and LDLR.

    Main Outcomes and Measures  Odds ratios (ORs) for type 2 diabetes and coronary artery disease.

    Results  Low-density lipoprotein cholesterol–lowering genetic variants at NPC1L1 were inversely associated with coronary artery disease (OR for a genetically predicted 1-mmol/L [38.7-mg/dL] reduction in LDL-C of 0.61 [95% CI, 0.42-0.88]; P = .008) and directly associated with type 2 diabetes (OR for a genetically predicted 1-mmol/L reduction in LDL-C of 2.42 [95% CI, 1.70-3.43]; P < .001). For PCSK9 genetic variants, the OR for type 2 diabetes per 1-mmol/L genetically predicted reduction in LDL-C was 1.19 (95% CI, 1.02-1.38; P = .03). For a given reduction in LDL-C, genetic variants were associated with a similar reduction in coronary artery disease risk (I2 = 0% for heterogeneity in genetic associations; P = .93). However, associations with type 2 diabetes were heterogeneous (I2 = 77.2%; P = .002), indicating gene-specific associations with metabolic risk of LDL-C-lowering alleles.

    Conclusions and Relevance  In this meta-analysis, exposure to LDL-C-lowering genetic variants in or near NPC1L1 and other genes was associated with a higher risk of type 2 diabetes. These data provide insights into potential adverse effects of LDL-C-lowering therapy.

  • 11. Norman, Mikael
    et al.
    Hallberg, Boubou
    Abrahamsson, Thomas
    Bjorklund, Lars J.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Farooqi, Aijaz
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bruun, Cathrine Foyn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gadsboll, Christian
    Hellstrom-Westas, Lena
    Ingemansson, Fredrik
    Kallen, Karin
    Ley, David
    Marsal, Karel
    Normann, Erik
    Serenius, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stephansson, Olof
    Stigson, Lennart
    Um-Bergstrom, Petra
    Håkansson, Stellan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Association Between Year of Birth and 1-Year Survival Among Extremely Preterm Infants in Sweden During 2004-2007 and 2014-20162019In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 321, no 12, p. 1188-1199Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown.

    OBJECTIV: To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016.

    DESIGN, SETTING AND PARTICIPANTS: All births at 22-26weeks' gestational age (n = 2205) between April 1, 2004, and March 31, 2007, and between January 1, 2014, and December 31, 2016, in Sweden were studied. Prospective data collection was used during 2004-2007. Data were obtained from the Swedish pregnancy, medical birth, and neonatal quality registries during 2014-2016. EXPOSURES Delivery at 22-26 weeks' gestational age.

    MAIN OUTCOMES AND MEASURES: The primary outcomewas infant survival to the age of 1 year. The secondary outcome was 1-year survival among live-born infants who did not have any major neonatal morbidity (specifically, without intraventricular hemorrhage grade 3-4, cystic periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity stage 3-5, or severe bronchopulmonary dysplasia).

    RESULTS: During 2004-2007, 1009 births (3.3/1000 of all births) occurred at 22-26 weeks' gestational age compared with 1196 births (3.4/1000 of all births) during 2014-2016 (P =.61). One-year survival among live-born infants at 22-26 weeks' gestational age was significantly lower during 2004-2007 (497 of 705 infants [70%]) than during 2014-2016 (711 of 923 infants [77%]) (difference, -7%[95% CI, -11% to -2.2%], P =.003). One-year survival among live-born infants at 22-26 weeks' gestational age and without any major neonatal morbidity was significantly lower during 2004-2007 (226 of 705 infants [32%]) than during 2014-2016 (355 of 923 infants [38%]) (difference, -6%[95% CI, -11% to -1.7%], P =.008).

    CONCLUSIONS AND RELEVANCE: Among live births at 22-26 weeks' gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.

  • 12. Okin, Peter M
    et al.
    Wachtell, Kristian
    Devereux, Richard B
    Harris, Katherine E
    Jern, Sverker
    Kjeldsen, Sverre E
    Julius, Stevo
    Lindholm, Lars H
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Nieminen, Markku S
    Edelman, Jonathan M
    Hille, Darcy A
    Dahlöf, Björn
    Regression of electrocardiographic left ventricular hypertrophy and decreased incidence of new-onset atrial fibrillation in patients with hypertension2006In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 296, no 10, p. 1242-1248Article in journal (Refereed)
    Abstract [en]

    Context Atrial fibrillation (AF) is associated with increased risk of mortality and cardiovascular events, particularly stroke, making prevention of new-onset AF a clinical priority. Although the presence and severity of electrocardiographic left ventricular hypertrophy (LVH) appear to predict development of AF, whether regression of electrocardiographic LVH is associated with a decreased incidence of AF is unclear. Objective To test the hypothesis that in-treatment regression or continued absence of electrocardiographic LVH during antihypertensive therapy is associated with a decreased incidence of AF, independent of blood pressure and treatment modality. Design, Setting, and Participants Double-blind, randomized, parallel-group study conducted in 1995-2001 among 8831 men and women with hypertension, aged 55-80 years (median, 67 years), with electrocardiographic LVH by Cornell voltage-duration product or Sokolow-Lyon voltage, with no history of AF, without AF on the baseline electrocardiogram, and enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension Study. Interventions Losartan-or atenolol-based treatment regimens, with follow-up assessments at 6 months and then yearly until death or study end. Main Outcome Measure New-onset AF in relation to electrocardiographic LVH determined at baseline and subsequently. Electrocardiographic LVH was measured using sex-adjusted Cornell product criteria ({R-aVL + S-V3 [+6 mm in women]} X QRS duration). Results After a mean (SD) follow-up of 4.7 (1.1) years, new-onset AF occurred in 290 patients with in-treatment regression or continued absence of Cornell product LVH for a rate of 14.9 per 1000 patient-years and in 411 patients with in-treatment persistence or development of LVH by Cornell product criteria for a rate of 19.0 per 1000 patient-years. In time-dependent Cox analyses adjusted for treatment effects, baseline differences in risk factors for AF, baseline and in-treatment blood pressure, and baseline severity of electrocardiographic LVH, lower in-treatment Cornell product LVH treated as a time-varying covariate was associated with a 12.4% lower rate of new-onset AF (adjusted hazard ratio [HR], 0.88; 95% CI, 0.80-0.97; P = .007) for every 1050 mm X msec (per 1-SD) lower Cornell product, with persistence of the benefit of losartan vs atenolol therapy on developing AF (HR, 0.83; 95% CI, 0.71-0.97; P = .01). Conclusions Lower Cornell product electrocardiographic LVH during antihypertensive therapy is associated with a lower likelihood of new-onset AF, independent of blood pressure lowering and treatment modality in essential hypertension. These findings suggest that antihypertensive therapy targeted at regression or prevention of electrocardiographic LVH may reduce the incidence of new-onset AF.

  • 13.
    Serenius, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Uppsala Univ, Dept Womens & Childrens Hlth, Sect Pediat, S-75185 Uppsala, Sweden.
    Kallen, Karin
    Blennow, Mats
    Ewald, Uwe
    Fellman, Vineta
    Holmstrom, Gerd
    Lindberg, Eva
    Lundqvist, Pia
    Marsal, Karel
    Norman, Mikael
    Olhager, Elisabeth
    Stigson, Lennart
    Stjernqvist, Karin
    Vollmer, Brigitte
    Stromberg, Bo
    Neurodevelopmental Outcome in Extremely Preterm Infants at 2.5 Years After Active Perinatal Care in Sweden2013In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 309, no 17, p. 1810-1820Article in journal (Refereed)
    Abstract [en]

    Importance Active perinatal care increases survival of extremely preterm infants; however, improved survival might be associated with increased disability among survivors. Objective To determine neurodevelopmental outcome in extremely preterm children at 2.5 years (corrected age). Design, Setting, and Participants Population-based prospective cohort of consecutive extremely preterm infants born before 27 weeks of gestation in Sweden between 2004 and 2007. Of 707 live-born infants, 491 (69%) survived to 2.5 years. Survivors were assessed and compared with singleton control infants who were born at term and matched by sex, ethnicity, and municipality. Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences. Main Outcomes and Measures Cognitive, language, and motor development was assessed with Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-III), which are standardized to mean (SD) scores of 100 (15). Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments. Assessments were made by week of gestational age. Results At a median age of 30.5 months (corrected), 456 of 491 (94%) extremely preterm children were evaluated (41 by chart review only). For controls, 701 had information on health status and 366 had Bayley-III assessments. Mean (SD) composite Bayley-III scores (cognition, 94 [12.3]; language, 98 [16.5]; motor, 94 [15.9]) were lower than the corresponding mean scores for controls (cognition, 104 [10.6]; P < .001; adjusted difference in mean scores, 9.2 [99% CI, 6.9-11.5]; language, 109 [12.3]; P < .001; adjusted difference in mean scores, 9.3 [99% Cl, 6.4-12.3]; and motor, 107 [13.7]; P < .001; adjusted difference in mean scores, 12.6 [99% Cl, 9.5-15.6]). Cognitive disability was moderate in 5% of the extremely preterm group vs 0.3% in controls (P < .001) and it was severe in 6.3% of the extremely preterm group vs 0.3% in controls (P < .001). Language disability was moderate in 9.4% of the extremely preterm group vs 2.5% in controls (P < .001) and severe in 6.6% of the extremely preterm group vs 0% in controls (P < .001). Other comparisons between the extremely preterm group vs controls were for cerebral palsy (7.0% vs 0.1%; P < .001), for blindness (0.9% vs 0%; P = .02), and for hearing impairment (moderate and severe, 0.9% vs 0%; P = .02, respectively). Overall, 42% (99% CI, 36%-48%) of extremely preterm children had no disability, 31% (99% CI, 25%-36%) had mild disability, 16% (99% CI, 12%-21%) had moderate disability, and 11% (99% CI, 7.2%-15%) had severe disability. Moderate or severe overall disability decreased with gestational age at birth (22 weeks, 60%; 23 weeks, 51%; 24 weeks, 34%; 25 weeks, 27%; and 26 weeks, 17%; P for trend < .001). Conclusions and Relevance Of children born extremely preterm and receiving active perinatal care, 73% had mild or no disability and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling families facing extremely preterm birth. JAMA. 2013;309(17):1810-1820

  • 14. van Meurs, Joyce B J
    et al.
    Trikalinos, Thomas A
    Ralston, Stuart H
    Balcells, Susana
    Brandi, Maria Luisa
    Brixen, Kim
    Kiel, Douglas P
    Langdahl, Bente L
    Lips, Paul
    Ljunggren, Osten
    Lorenc, Roman
    Obermayer-Pietsch, Barbara
    Ohlsson, Claes
    Pettersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Reid, David M
    Rousseau, Francois
    Scollen, Serena
    Van Hul, Wim
    Agueda, Lidia
    Akesson, Kristina
    Benevolenskaya, Lidia I
    Ferrari, Serge L
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hofman, Albert
    Husted, Lise Bjerre
    Kruk, Marcin
    Kaptoge, Stephen
    Karasik, David
    Karlsson, Magnus K
    Lorentzon, Mattias
    Masi, Laura
    McGuigan, Fiona E A
    Mellström, Dan
    Mosekilde, Leif
    Nogues, Xavier
    Pols, Huibert A P
    Reeve, Jonathan
    Renner, Wilfried
    Rivadeneira, Fernando
    van Schoor, Natasja M
    Weber, Kurt
    Ioannidis, John P A
    Uitterlinden, André G
    Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis.2008In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 299, no 11, p. 1277-1290Article in journal (Refereed)
    Abstract [en]

    Context: Mutations in the low-density lipoprotein receptor–related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population.

    Objective: To generate large-scale evidence on whether 2 common variants ofLRP5 (Val667Met, Ala1330Val) and 1 variant of LRP6 (Ile1062Val) are associated with BMD and fracture risk.

    Design and Setting: Prospective, multicenter, collaborative study of individual-level data on 37 534 individuals from 18 participating teams in Europe and North America. Data were collected between September 2004 and January 2007; analysis of the collected data was performed between February and May 2007. Bone mineral density was assessed by dual-energy x-ray absorptiometry. Fractures were identified via questionnaire, medical records, or radiographic documentation; incident fracture data were available for some cohorts, ascertained via routine surveillance methods, including radiographic examination for vertebral fractures.

    Main Outcome Measures: Bone mineral density of the lumbar spine and femoral neck; prevalence of all fractures and vertebral fractures.

    Results: The Met667 allele of LRP5 was associated with reduced lumbar spine BMD (n = 25 052 [number of participants with available data]; 20-mg/cm2 lower BMD per Met667 allele copy; P = 3.3 × 10−8), as was the Val1330 allele (n = 24 812; 14-mg/cm2 lower BMD per Val1330 copy; P = 2.6 × 10−9). Similar effects were observed for femoral neck BMD, with a decrease of 11 mg/cm2(P = 3.8 × 10−5) and 8 mg/cm2 (P = 5.0 × 10−6) for the Met667 and Val1330 alleles, respectively (n = 25 193). Findings were consistent across studies for bothLRP5 alleles. Both alleles were associated with vertebral fractures (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.08-1.47 for Met667 [2001 fractures among 20 488 individuals] and OR, 1.12; 95% CI, 1.01-1.24 for Val1330 [1988 fractures among 20 096 individuals]). Risk of all fractures was also increased with Met667 (OR, 1.14; 95% CI, 1.05-1.24 per allele [7876 fractures among 31 435 individuals)]) and Val1330 (OR, 1.06; 95% CI, 1.01-1.12 per allele [7802 fractures among 31 199 individuals]). Effects were similar when adjustments were made for age, weight, height, menopausal status, and use of hormone therapy. Fracture risks were partly attenuated by adjustment for BMD. Haplotype analysis indicated that Met667 and Val1330 variants both independently affected BMD. The LRP6Ile1062Val polymorphism was not associated with any osteoporosis phenotype. All aforementioned associations except that between Val1330 and all fractures and vertebral fractures remained significant after multiple-comparison adjustments.

    Conclusions: Common LRP5 variants are consistently associated with BMD and fracture risk across different white populations. The magnitude of the effect is modest. LRP5 may be the first gene to reach a genome-wide significance level (a conservative level of significance [herein, unadjusted P < 10−7] that accounts for the many possible comparisons in the human genome) for a phenotype related to osteoporosis.

1 - 14 of 14
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf