RT Journal Article
SR Electronic
T1 Genetic correlations among neuro-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 Jiayin Sun
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 Nejentsev
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 Eva Ellinghaus
A1 James T. Elder
A1 Lam C. Tsoi
A1 Richard C. Trembath
A1 Jonathan N. Barker
A1 Andre Franke
A1 Abbas Dehghan
A1 The 23andMe Research Team
A1 The Inflammation Working Group of the CHARGE Consortium, The METASTROKE Consortium of the International Stroke Genetics Consortium, The Netherlands Twin Registry, The neuroCHARGE Working Group
A1 Stephen V. Faraone
A1 Stephen J. Glatt
YR 2017
UL http://biorxiv.org/content/early/2017/08/13/070730.abstract
AB Evidence of elevated autoimmune comorbidity and altered immune signaling has been observed in samples of individuals affected by neuropsychiatric disorders. It remains unclear whether these altered immunological states have a genetic basis. The present study sought to use existing summary-level data generated from previous genome-wide association studies (GWASs) in order to explore whether common variant genetic risk factors (i.e., SNPs) are shared between a set of neuro-behavioral phenotypes and a set of immune-inflammatory phenotypes. For each phenotype, we calculated the estimated heritability and examined pair-wise genetic correlations using the LD score regression method. We observed significant positive genetic correlations between bipolar disorder and each of: celiac disease (rg = 0.31 ± 0.09, uncorrected p = 4.0×10−4), Crohn’s disease (rg = 0.21 ± 0.05, uncorrected p = 3.7×10−5), and ulcerative colitis (rg = 0.23 ± 0.06, uncorrected p = 2.0×10−4). We observed significant positive correlations between schizophrenia and each of: Crohn’s disease (rg = 0.12 ± 0.03, uncorrected p = 3.0×10−4), ulcerative colitis (rg = 0.13 ± 0.04, uncorrected p = 4.0×10−4), primary biliary cirrhosis (rg = 0.15 ± 0.05, uncorrected p = 0.0012), and systemic lupus erythematous (rg = 0.14 ± 0.04, uncorrected p = 0.0013). We also found significant positive correlations between major depression and hypothyroidism (rg = 0.33 ± 0.09, uncorrected p = 5×10−4) and between Tourette syndrome and allergy (rg = 0.24 ± 0.06, uncorrected p =2.7×10−5). We highlight genes mapping near the top single nucleotide polymorphisms (SNPs) that may contribute to these behavior-immune correlations. We also observed many significant genetic correlations amongst the immune-inflammatory phenotypes that survived testing for multiple correction. We discuss these results in the context of clinical epidemiologic literature and other genomic approaches and discuss important limitations and caveats of the LD score regression approach we utilized. These results shed new light on the immunogenetics of psychiatric disorders and suggest that similarities in a polygenic diathesis may contribute to increased comorbidity between psychiatric and immune-related disorders.