RT Journal Article SR Electronic T1 Using genotype data to distinguish pleiotropy from heterogeneity: deciphering coheritability in autoimmune and neuropsychiatric diseases JF bioRxiv FD Cold Spring Harbor Laboratory SP 030783 DO 10.1101/030783 A1 Buhm Han A1 Jennie G Pouget A1 Kamil Slowikowski A1 Eli Stahl A1 Cue Hyunkyu Lee A1 Dorothee Diogo A1 Xinli Hu A1 Yu Rang Park A1 Eunji Kim A1 Peter K Gregersen A1 Solbritt Rantapää Dahlqvist A1 Jane Worthington A1 Javier Martin A1 Steve Eyre A1 Lars Klareskog A1 Tom Huizinga A1 Wei-Min Chen A1 Suna Onengut-Gumuscu A1 Stephen S Rich A1 Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium A1 Naomi Wray A1 Soumya Raychaudhuri YR 2015 UL http://biorxiv.org/content/early/2015/11/06/030783.abstract AB Shared genetic architecture between phenotypes may be driven by a common genetic basis (pleiotropy) or a subset of genetically similar individuals (heterogeneity). We developed BUHMBOX, a well-powered statistical method to distinguish pleiotropy from heterogeneity using genotype data. We observed a shared genetic basis between 11 of 17 tested autoimmune diseases and type I diabetes (T1D, p<10−12) and 11 of 17 tested autoimmune diseases and rheumatoid arthritis (RA, p<10−7). This sharing could not be explained by heterogeneity (corrected pBUHMBOX>0.2 using 6,670 T1D cases and 7,279 RA cases), suggesting that shared genetic features in autoimmunity are due to pleiotropy. We observed a shared genetic basis between seronegative and seropostive RA (p<10−22), explained by heterogeneity (pBUHMBOX=0.008 in 2,406 seronegative RA cases). Consistent with previous observations, we observed genetic sharing between major depressive disorder (MDD) and schizophrenia (p<10−9). This sharing is not explained by heterogeneity (pBUHMBOX=0.28 in 9,238 MDD cases).