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 â '4) and for 11 autoimmune diseases and rheumatoid arthritis (RA; P < 1 × 10 â '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 × 10 â '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 × 10 â '4) that was not explained by subgroup heterogeneity (P BUHMBOX = 0.28; 9,238 MDD cases).
CITATION STYLE
Han, B., Pouget, J. G., Slowikowski, K., Stahl, E., Lee, C. H., Diogo, D., … Raychaudhuri, S. (2016). A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases. Nature Genetics, 48(7), 803–810. https://doi.org/10.1038/ng.3572
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