A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases.
Authors | |
Abstract | 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 × 10(-4)) and for 11 autoimmune diseases and rheumatoid arthritis (RA; P 1 × 10(-3)). This sharing was not explained by subgroup heterogeneity (corrected PBUHMBOX > 0.2; 6,670 T1D cases and 7,279 RA cases). Genetic sharing between seronegative and seropostive RA (P 1 × 10(-9)) had significant evidence of subgroup heterogeneity, suggesting a subgroup of seropositive-like cases within seronegative cases (PBUHMBOX = 0.008; 2,406 seronegative RA cases). We also observed a shared genetic basis for major depressive disorder (MDD) and schizophrenia (P 1 × 10(-4)) that was not explained by subgroup heterogeneity (PBUHMBOX = 0.28; 9,238 MDD cases). |
Year of Publication | 2016
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Journal | Nat Genet
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Volume | 48
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Issue | 7
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Pages | 803-10
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Date Published | 2016 Jul
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ISSN | 1546-1718
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URL | |
DOI | 10.1038/ng.3572
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PubMed ID | 27182969
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PubMed Central ID | PMC4925284
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Links | |
Grant list | U19 AI111224 / AI / NIAID NIH HHS / United States
T32 HG002295 / HG / NHGRI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
U01 GM092691 / GM / NIGMS NIH HHS / United States
U01 DK062418 / DK / NIDDK NIH HHS / United States
R01 AR063759 / AR / NIAMS NIH HHS / United States
UH2 AR067677 / AR / NIAMS NIH HHS / United States
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