American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2018
Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Tylee Daniel S, Sun Jiayin, Hess Jonathan L, Tahir Muhammad A, Sharma Esha, Malik Rainer, Worrall Bradford B, Levine Andrew J, Martinson Jeremy J, Nejentsev Sergey, Speed Doug, Fischer Annegret, Mick Eric, Walker Brian R, Crawford Andrew, Grant Struan F A, Polychronakos Constantin, Bradfield Jonathan P, Sleiman Patrick M A, Hakonarson Hakon, Ellinghaus Eva, Elder James T, Tsoi Lam C, Trembath Richard C, Barker Jonathan N, Franke Andre, Dehghan Abbas, 23 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, Faraone Stephen V, Glatt Stephen J
Аннотация
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.