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  • 1. Forouhi, Nita G.
    et al.
    Imamura, Fumiaki
    Sharp, Stephen J.
    Koulman, Albert
    Schulze, Matthias B.
    Zheng, Jusheng
    Ye, Zheng
    Sluijs, Ivonne
    Guevara, Marcela
    Maria Huerta, Jose
    Kroeger, Janine
    Wang, Laura Yun
    Summerhill, Keith
    Griffin, Julian L.
    Feskens, Edith J. M.
    Affret, Aurelie
    Amiano, Pilar
    Boeing, Heiner
    Dow, Courtney
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund University, Malmö, Sweden.
    Gonzalez, Carlos
    Kaaks, Rudolf
    Key, Timothy J.
    Khaw, Kay Tee
    Kuehn, Tilman
    Mortensen, Lotte Maxild
    Nilsson, Peter M.
    Overvad, Kim
    Pala, Valeria
    Palli, Domenico
    Panico, Salvatore
    Ramon Quiros, J.
    Rodriguez-Barranco, Miguel
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Scalbert, Augustin
    Slimani, Nadia
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tormo, Maria-Jose
    Tumino, Rosario
    van der A, Daphne L.
    van der Schouw, Yvonne T.
    Langenberg, Claudia
    Riboli, Elio
    Wareham, Nicholas J.
    Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study2016Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 13, nr 7, artikel-id e1002094Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations.

    Methods and Findings Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, a-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88-0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77-0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85-0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with.-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs.

    Conclusions These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.

  • 2. Fuchsberger, Christian
    et al.
    Flannick, Jason
    Teslovich, Tanya M.
    Mahajan, Anubha
    Agarwala, Vineeta
    Gaulton, Kyle J.
    Ma, Clement
    Fontanillas, Pierre
    Moutsianas, Loukas
    McCarthy, Davis J.
    Rivas, Manuel A.
    Perry, John R. B.
    Sim, Xueling
    Blackwell, Thomas W.
    Robertson, Neil R.
    Rayner, N. William
    Cingolani, Pablo
    Locke, Adam E.
    Tajes, Juan Fernandez
    Highland, Heather M.
    Dupuis, Josee
    Chines, Peter S.
    Lindgren, Cecilia M.
    Hartl, Christopher
    Jackson, Anne U.
    Chen, Han
    Huyghe, Jeroen R.
    van de Bunt, Martijn
    Pearson, Richard D.
    Kumar, Ashish
    Mueller-Nurasyid, Martina
    Grarup, Niels
    Stringham, Heather M.
    Gamazon, Eric R.
    Lee, Jaehoon
    Chen, Yuhui
    Scott, Robert A.
    Below, Jennifer E.
    Chen, Peng
    Huang, Jinyan
    Go, Min Jin
    Stitzel, Michael L.
    Pasko, Dorota
    Parker, Stephen C. J.
    Varga, Tibor V.
    Green, Todd
    Beer, Nicola L.
    Day-Williams, Aaron G.
    Ferreira, Teresa
    Fingerlin, Tasha
    Horikoshi, Momoko
    Hu, Cheng
    Huh, Iksoo
    Ikram, Mohammad Kamran
    Kim, Bong-Jo
    Kim, Yongkang
    Kim, Young Jin
    Kwon, Min-Seok
    Lee, Juyoung
    Lee, Selyeong
    Lin, Keng-Han
    Maxwell, Taylor J.
    Nagai, Yoshihiko
    Wang, Xu
    Welch, Ryan P.
    Yoon, Joon
    Zhang, Weihua
    Barzilai, Nir
    Voight, Benjamin F.
    Han, Bok-Ghee
    Jenkinson, Christopher P.
    Kuulasmaa, Teemu
    Kuusisto, Johanna
    Manning, Alisa
    Ng, Maggie C. Y.
    Palmer, Nicholette D.
    Balkau, Beverley
    Stancakova, Alena
    Abboud, Hanna E.
    Boeing, Heiner
    Giedraitis, Vilmantas
    Prabhakaran, Dorairaj
    Gottesman, Omri
    Scott, James
    Carey, Jason
    Kwan, Phoenix
    Grant, George
    Smith, Joshua D.
    Neale, Benjamin M.
    Purcell, Shaun
    Butterworth, Adam S.
    Howson, Joanna M. M.
    Lee, Heung Man
    Lu, Yingchang
    Kwak, Soo-Heon
    Zhao, Wei
    Danesh, John
    Lam, Vincent K. L.
    Park, Kyong Soo
    Saleheen, Danish
    So, Wing Yee
    Tam, Claudia H. T.
    Afzal, Uzma
    Aguilar, David
    Arya, Rector
    Aung, Tin
    Chan, Edmund
    Navarro, Carmen
    Cheng, Ching-Yu
    Palli, Domenico
    Correa, Adolfo
    Curran, Joanne E.
    Rybin, Denis
    Farook, Vidya S.
    Fowler, Sharon P.
    Freedman, Barry I.
    Griswold, Michael
    Hale, Daniel Esten
    Hicks, Pamela J.
    Khor, Chiea-Chuen
    Kumar, Satish
    Lehne, Benjamin
    Thuillier, Dorothee
    Lim, Wei Yen
    Liu, Jianjun
    van der Schouw, Yvonne T.
    Loh, Marie
    Musani, Solomon K.
    Puppala, Sobha
    Scott, William R.
    Yengo, Loic
    Tan, Sian-Tsung
    Taylor, Herman A., Jr.
    Thameem, Farook
    Wilson, Gregory, Sr.
    Wong, Tien Yin
    Njolstad, Pal Rasmus
    Levy, Jonathan C.
    Mangino, Massimo
    Bonnycastle, Lori L.
    Schwarzmayr, Thomas
    Fadista, Joao
    Surdulescu, Gabriela L.
    Herder, Christian
    Groves, Christopher J.
    Wieland, Thomas
    Bork-Jensen, Jette
    Brandslund, Ivan
    Christensen, Cramer
    Koistinen, Heikki A.
    Doney, Alex S. F.
    Kinnunen, Leena
    Esko, Tonu
    Farmer, Andrew J.
    Hakaste, Liisa
    Hodgkiss, Dylan
    Kravic, Jasmina
    Lyssenko, Valeriya
    Hollensted, Mette
    Jorgensen, Marit E.
    Jorgensen, Torben
    Ladenvall, Claes
    Justesen, Johanne Marie
    Karajamaki, Annemari
    Kriebel, Jennifer
    Rathmann, Wolfgang
    Lannfelt, Lars
    Lauritzen, Torsten
    Narisu, Narisu
    Linneberg, Allan
    Melander, Olle
    Milani, Lili
    Neville, Matt
    Orho-Melander, Marju
    Qi, Lu
    Qi, Qibin
    Roden, Michael
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Swift, Amy
    Rosengren, Anders H.
    Stirrups, Kathleen
    Wood, Andrew R.
    Mihailov, Evelin
    Blancher, Christine
    Carneiro, Mauricio O.
    Maguire, Jared
    Poplin, Ryan
    Shakir, Khalid
    Fennell, Timothy
    DePristo, Mark
    de Angelis, Martin Hrabe
    Deloukas, Panos
    Gjesing, Anette P.
    Jun, Goo
    Nilsson, Peter
    Murphy, Jacquelyn
    Onofrio, Robert
    Thorand, Barbara
    Hansen, Torben
    Meisinger, Christa
    Hu, Frank B.
    Isomaa, Bo
    Karpe, Fredrik
    Liang, Liming
    Peters, Annette
    Huth, Cornelia
    O'Rahilly, Stephen P.
    Palmer, Colin N. A.
    Pedersen, Oluf
    Rauramaa, Rainer
    Tuomilehto, Jaakko
    Salomaa, Veikko
    Watanabe, Richard M.
    Syvanen, Ann-Christine
    Bergman, Richard N.
    Bharadwaj, Dwaipayan
    Bottinger, Erwin P.
    Cho, Yoon Shin
    Chandak, Giriraj R.
    Chan, Juliana C. N.
    Chia, Kee Seng
    Daly, Mark J.
    Ebrahim, Shah B.
    Langenberg, Claudia
    Elliott, Paul
    Jablonski, Kathleen A.
    Lehman, Donna M.
    Jia, Weiping
    Ma, Ronald C. W.
    Pollin, Toni I.
    Sandhu, Manjinder
    Tandon, Nikhil
    Froguel, Philippe
    Barroso, Ines
    Teo, Yik Ying
    Zeggini, Eleftheria
    Loos, Ruth J. F.
    Small, Kerrin S.
    Ried, Janina S.
    DeFronzo, Ralph A.
    Grallert, Harald
    Glaser, Benjamin
    Metspalu, Andres
    Wareham, Nicholas J.
    Walker, Mark
    Banks, Eric
    Gieger, Christian
    Ingelsson, Erik
    Im, Hae Kyung
    Illig, Thomas
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Lund University Diabetes Centre, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
    Buck, Gemma
    Trakalo, Joseph
    Buck, David
    Prokopenko, Inga
    Magi, Reedik
    Lind, Lars
    Farjoun, Yossi
    Owen, Katharine R.
    Gloyn, Anna L.
    Strauch, Konstantin
    Tuomi, Tiinamaija
    Kooner, Jaspal Singh
    Lee, Jong-Young
    Park, Taesung
    Donnelly, Peter
    Morris, Andrew D.
    Hattersley, Andrew T.
    Bowden, Donald W.
    Collins, Francis S.
    Atzmon, Gil
    Chambers, John C.
    Spector, Timothy D.
    Laakso, Markku
    Strom, Tim M.
    Bell, Graeme I.
    Blangero, John
    Duggirala, Ravindranath
    Tai, E. Shyong
    McVean, Gilean
    Hanis, Craig L.
    Wilson, James G.
    Seielstad, Mark
    Frayling, Timothy M.
    Meigs, James B.
    Cox, Nancy J.
    Sladek, Rob
    Lander, Eric S.
    Gabriel, Stacey
    Burtt, Noel P.
    Mohlke, Karen L.
    Meitinger, Thomas
    Groop, Leif
    Abecasis, Goncalo
    Florez, Jose C.
    Scott, Laura J.
    Morris, Andrew P.
    Kang, Hyun Min
    Boehnke, Michael
    Altshuler, David
    McCarthy, Mark I.
    The genetic architecture of type 2 diabetes2016Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 536, nr 7614, s. 41-47Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.

  • 3. Kengne, Andre Pascal
    et al.
    Beulens, Joline W. J.
    Peelen, Linda M.
    Moons, Karel G. M.
    van der Schouw, Yvonne T.
    Schulze, Matthias B.
    Spijkerman, Annemieke M. W.
    Griffin, Simon J.
    Grobbee, Diederick E.
    Palla, Luigi
    Tormo, Maria-Jose
    Arriola, Larraitz
    Barengo, Noel C.
    Barricarte, Aurelio
    Boeing, Heiner
    Bonet, Catalina
    Clavel-Chapelon, Francoise
    Dartois, Laureen
    Fagherazzi, Guy
    Franks, Paul W.
    Maria Huerta, Jose
    Kaaks, Rudolf
    Key, Timothy J.
    Khaw, Kay Tee
    Li, Kuanrong
    Muehlenbruch, Kristin
    Nilsson, Peter M.
    Overvad, Kim
    Overvad, Thure F.
    Palli, Domenico
    Panico, Salvatore
    Ramon Quiros, J.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Roswall, Nina
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Tagliabue, Giovanna
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne L.
    Forouhi, Nita G.
    Sharp, Stephen J.
    Langenberg, Claudia
    Riboli, Elio
    Wareham, Nicholas J.
    Non-invasive risk scores for prediction of type 2 diabetes (EPIC-InterAct): a validation of existing models2014Ingår i: Lancet Diabetes & Endocrinology, ISSN 2213-8587, Vol. 2, nr 1, s. 19-29Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The comparative performance of existing models for prediction of type 2 diabetes across populations has not been investigated. We validated existing non-laboratory-based models and assessed variability in predictive performance in European populations. Methods We selected non-invasive prediction models for incident diabetes developed in populations of European ancestry and validated them using data from the EPIC-InterAct case-cohort sample (27 779 individuals from eight European countries, of whom 12 403 had incident diabetes). We assessed model discrimination and calibration for the first 10 years of follow-up. The models were first adjusted to the country-specific diabetes incidence. We did the main analyses for each country and for subgroups defined by sex, age (<60 years vs >= 60 years), BMI (<25 kg/m(2) vs >= 25 kg/m(2)), and waist circumference (men <102 cm vs >= 102 cm; women <88 cm vs >= 88 cm). Findings We validated 12 prediction models. Discrimination was acceptable to good: C statistics ranged from 0.76 (95% CI 0.72-0.80) to 0.81 (0.77-0.84) overall, from 0.73 (0.70-0.76) to 0.79 (0.74-0.83) in men, and from 0.78 (0.74-0.82) to 0.81 (0.80-0.82) in women. We noted significant heterogeneity in discrimination (p(heterogeneity) <0.0001) in all but one model. Calibration was good for most models, and consistent across countries (p(heterogeneity) >0.05) except for three models. However, two models overestimated risk, DPoRT by 34% (95% CI 29-39%) and Cambridge by 40% (28-52%). Discrimination was always better in individuals younger than 60 years or with a low waist circumference than in those aged at least 60 years or with a large waist circumference. Patterns were inconsistent for BMI. All models overestimated risks for individuals with a BMI of <25 kg/m(2). Calibration patterns were inconsistent for age and waist-circumference subgroups. Interpretation Existing diabetes prediction models can be used to identify individuals at high risk of type 2 diabetes in the general population. However, the performance of each model varies with country, age, sex, and adiposity.

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