PT  - JOURNAL ARTICLE
AU  - Buhm Han
AU  - Jennie G Pouget
AU  - Kamil Slowikowski
AU  - Eli Stahl
AU  - Cue Hyunkyu Lee
AU  - Dorothee Diogo
AU  - Xinli Hu
AU  - Yu Rang Park
AU  - Eunji Kim
AU  - Peter K Gregersen
AU  - Solbritt Rantapää Dahlqvist
AU  - Jane Worthington
AU  - Javier Martin
AU  - Steve Eyre
AU  - Lars Klareskog
AU  - Tom Huizinga
AU  - Wei-Min Chen
AU  - Suna Onengut-Gumuscu
AU  - Stephen S Rich
AU  - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
AU  - Naomi Wray
AU  - Soumya Raychaudhuri
TI  - Using genotype data to distinguish pleiotropy from heterogeneity: deciphering coheritability in autoimmune and neuropsychiatric diseases
AID  - 10.1101/030783
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 030783
4099  - http://biorxiv.org/content/early/2015/11/06/030783.short
4100  - http://biorxiv.org/content/early/2015/11/06/030783.full
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).