Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data.

TitleGenetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data.
Publication TypeJournal Article
Year of Publication2018
AuthorsTylee DS, Sun J, Hess JL, Tahir MA, Sharma E, Malik R, Worrall BB, Levine AJ, Martinson JJ, Nejentsev S, Speed D, Fischer A, Mick E, Walker BR, Crawford A, Grant SFA, Polychronakos C, Bradfield JP, Sleiman PMA, Hakonarson H, Ellinghaus E, Elder JT, Tsoi LC, Trembath RC, Barker JN, Franke A, Dehghan A, Faraone SV, Glatt SJ
Corporate Authors23 and Me Research Team, Inflammation Working Group of the CHARGE Consortium, METASTROKE Consortium of the International Stroke Genetics Consortium, Netherlands Twin Registry, neuroCHARGE Working Group, Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium
JournalAm J Med Genet B Neuropsychiatr Genet
Date Published2018 Oct 16

Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune-related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit-hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome-wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune-related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.

Alternate JournalAm. J. Med. Genet. B Neuropsychiatr. Genet.
PubMed ID30325587
Grant ListR03 DA026099 / DA / NIDA NIH HHS / United States
AI2869; AJL / / UCLA Center for AIDS Research /
SJG / / National Alliance for Research on Schizophrenia and Depression /
SJG / / Sidney R. Baer, Jr. Foundation /
SJG / / Brain and Behavior Research Foundation /
Weatherstone Pre-doctoral Training Grant #9645; DS / / Autism Speaks / United States
SJG / / Gerber Foundation /
R01MH101519, R01AG054002, P50MH081755 (SJG), R03DA / / National Institutes of Health /
R01 AG054002 / AG / NIA NIH HHS / United States
SN / / NIHR Cambridge Biomedical Research Centre /
R01 MH101519 / MH / NIMH NIH HHS / United States
RM / / Vascular Dementia Research Foundation /
SN / / Wellcome Trust / United Kingdom