Nature genetics · 2016
A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Han Buhm, Pouget Jennie G, Slowikowski Kamil, Stahl Eli, Lee Cue Hyunkyu, Diogo Dorothee, Hu Xinli, Park Yu Rang, Kim Eunji, Gregersen Peter K, Dahlqvist Solbritt Rantapää, Worthington Jane, Martin Javier, Eyre Steve, Klareskog Lars, Huizinga Tom, Chen Wei-Min, Onengut-Gumuscu Suna, Rich Stephen S, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Wray Naomi R, Raychaudhuri Soumya
Аннотация
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).