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

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

来源:bioRxiv_logobioRxiv
英文摘要

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 (GWASs) to determine if commonly varying single nucleotide polymorphisms (SNPs) 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 (HESS) 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 amongst 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.

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

10.1101/070730

神经病学、精神病学遗传学基础医学

allergyanorexia nervosaattention deficit-hyperactivity disorderautoimmune disorderbipolar disorderceliac diseasechildhood ear infectionC-reactive proteinCrohn’s diseasegenetic correlationgenome-wide associationhypothyroidismmajor depressionneuroticismobsessive schizophreniaprimary biliary cirrhosisrheumatoid arthritissmokingsystemic lupus erythematosusTourette syndrometuberculosis susceptibilitytype 1 diabetesulcerative colitis

Sun Jiayin,Tahir Muhammad A.,Malik Rainer,Levine Andrew J.,Martinson Jeremy J.,Nejentsev Sergey,Mick Eric,Polychronakos Constantin,Ellinghaus Eva,Elder James T.,Trembath Richard C.,The 23andMe Research Team,Faraone Stephen V.,Glatt Stephen J.,Hakonarson Hakon,Barker Jonathan N.,Worrall Bradford B.,Sharma Esha,Sleiman Patrick M. A.,Walker Brian R.,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, The Eating Disorders Working Groups of the Psychiatric Genomics Consortium, The Obsessive Compulsive Disorder and Tourette Syndrome Working Group,Franke Andre,Grant Struan F.A.,Tylee Daniel S.,Hess Jonathan L.,Dehghan Abbas,Bradfield Jonathan P.,Speed Doug,Tsoi Lam C.,Crawford Andrew,Fischer Annegret.Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data[EB/OL].(2025-03-28)[2025-05-07].https://www.biorxiv.org/content/10.1101/070730.点此复制

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