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A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases
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2016 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, no 7, 803-+ p.Article in journal (Refereed) PublishedText
Abstract [en]

There is growing evidence of shared risk alleles for complex traits (pleiotropy), including autoimmune and neuropsychiatric diseases. This might be due to sharing among all individuals (whole-group pleiotropy) or a subset of individuals in a genetically heterogeneous cohort (subgroup heterogeneity). Here we describe the use of a well-powered statistic, BUHMBOX, to distinguish between those two situations using genotype data. We observed a shared genetic basis for 11 autoimmune diseases and type 1 diabetes (T1D; P < 1 x 10(-4)) and for 11 autoimmune diseases and rheumatoid arthritis (RA; P < 1 x 10(-3)). This sharing was not explained by subgroup heterogeneity (corrected P-BUHMBOX > 0.2; 6,670 T1D cases and 7,279 RA cases). Genetic sharing between seronegative and seropostive RA (P < 1 x 10(-9)) had significant evidence of subgroup heterogeneity, suggesting a subgroup of seropositive-like cases within seronegative cases (P-BUHMBOX = 0.008; 2,406 seronegative RA cases). We also observed a shared genetic basis for major depressive disorder (MDD) and schizophrenia (P < 1 x 10(-4)) that was not explained by subgroup heterogeneity (P-BUHMBOX = 0.28; 9,238 MDD cases).

Place, publisher, year, edition, pages
2016. Vol. 48, no 7, 803-+ p.
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Medical Genetics
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URN: urn:nbn:se:umu:diva-124226DOI: 10.1038/ng.3572ISI: 000378840100019PubMedID: 27182969OAI: oai:DiVA.org:umu-124226DiVA: diva2:950551
Available from: 2016-08-01 Created: 2016-07-28 Last updated: 2016-08-01Bibliographically approved

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Dahlqvist, Solbritt Rantapää
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Reumatology
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