RT Journal Article
SR Electronic
T1 Genetic correlations among brain-behavioral and immune-related phenotypes based on genome-wide association data
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 070730
DO 10.1101/070730
A1 Daniel S. Tylee
A1 Jonathan L. Hess
A1 Muhammad A. Tahir
A1 Esha Sharma
A1 Rainer Malik
A1 Bradford B. Worrall
A1 Andrew J. Levine
A1 Jeremy J. Martinson
A1 Sergey Nejenstev
A1 Doug Speed
A1 Annegret Fischer
A1 Eric Mick
A1 Brian R. Walker
A1 Andrew Crawford
A1 Struan F. A. Grant
A1 Constantin Polychronakos
A1 Jonathan P. Bradfield
A1 Patrick M. A. Sleiman
A1 Hakon Hakonarson
A1 The METASTROKE Consortium of the International Stroke Genetics Consortium
A1 The Netherlands Twin Registry
A1 The neuroCHARGE Working Group
A1 The Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium
A1 Stephen V. Faraone
A1 Stephen J. Glatt
YR 2016
UL http://biorxiv.org/content/early/2016/08/21/070730.abstract
AB Evidence of altered immune function and inflammatory signaling has been reported in samples of individuals affected by major psychiatric and neurodevelopmental disorders; it remains unclear how these altered immunological states arise, though a genetic basis has been postulated. The present study sought to use existing summary-level data generated from previous genome-wide association studies (GWAS) in order to explore whether common variant genetic risk factors might be shared between a set of psychiatric/neurodevelopmental phenotypes and a set of medical phenotypes enriched with immune and inflammatory processes. Based on the available GWAS summary data, we calculated the estimated heritability for each phenotype and we examined the genetic correlations between pair-wise combinations of phenotypes, using the LD Score Regression method. We observed positive genetic correlations between bipolar disorder and both celiac disease (rg = 0.31 ± 0.09) and ulcerative colitis (rg = 0.25 ± 0.06), which survived correction for multiple testing. We also observed several robust genetic correlations amongst the set of medical phenotypes enriched for immune and inflammatory processes. We review the relevant clinical literature and suggest that similarities in common variant genetic diatheses may contribute to increased comorbidity between bipolar and autoimmune/inflammatory conditions involving the gastrointestinal tract. We also discuss the limitations of the present approach and important caveats for interpreting the findings.