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

The METASTROKE Consortium of the International Stroke Genetics Consortium, The Netherlands Twin Registry, The neuroCHARGE Working Group, The Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium, The 23 and Me Research Team, The Inflammation Working Group of the CHARGE Consortium, Daniel S. Tylee*, Jiayin Sun, Jonathan L. Hess, Muhammad A. Tahir, Esha Sharma, Rainer Malik, Bradford B. Worrall, Andrew J. Levine, Jeremy J. Martinson, Sergey Nejentsev, Doug Speed, Annegret Fischer, Eric Mick, Brian R. WalkerAndrew Crawford, Struan F.A. Grant, Constantin Polychronakos, Jonathan P. Bradfield, Patrick M.A. Sleiman, Hakon Hakonarson, Eva Ellinghaus, James T. Elder, Lam C. Tsoi, Richard C. Trembath, Jonathan N. Barker, Andre Franke, Abbas Dehghan, Stephen V. Faraone, Stephen J. Glatt

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

132 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)641-657
Number of pages17
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume177
Issue number7
Early online date16 Oct 2018
DOIs
Publication statusPublished - Oct 2018

Keywords

  • allergy
  • anorexia nervosa
  • attention deficit-hyperactivity disorder
  • autoimmune disorder
  • bipolar disorder
  • C-reactive protein
  • celiac disease
  • childhood ear infection
  • Crohn's disease
  • genetic correlation
  • genome-wide association
  • hypothyroidism
  • major depression
  • neuroticism
  • obsessive schizophrenia
  • primary biliary cirrhosis
  • rheumatoid arthritis
  • smoking
  • systemic lupus erythematosus
  • Tourette syndrome
  • tuberculosis susceptibility
  • type 1 diabetes
  • ulcerative colitis

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