CC BY NC NDTylee, Daniel SSpeed, DougCrawford, AndrewGrant, Struan FASun, JiayinHess, Jonathan LTahir, Muhammad ASharma, EshaMalik, RainerWorrall, Bradford BLevine, Andrew JMartinson, Jeremy JNejentsev, SergeyFischer, AnnegretMick, EricWalker, Brian RPolychronakos, ConstantinBradfield, Jonathan PSleiman, Patrick MAHakonarson, HakonEllinghaus, EvaElder, James TTsoi, Lam CTrembath, Richard CBarker, Jonathan NFranke, AndreDehghan, AbbasTeam, The 23 and Me ResearchConsortium, The Inflammation Working Group of the CHARGEConsortium, The METASTROKE Consortium of the International Stroke GeneticsRegistry, The Netherlands TwinGroup, The neuroCHARGE WorkingConsortium, The Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric GenomicsFaraone, Stephen VGlatt, Stephen J2025-06-142025-06-142016-08-211552-48411552-485X10.1101/07073010.1002/ajmg.b.32652https://ror.circle-u.eu/handle/123456789/407320<jats:title>Abstract</jats:title><jats:p>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.</jats:p>OPENCrohn’s diseaserheumatoid arthritisMaleMedicine (General)Multifactorial InheritanceDatabases, Factualtype 1 diabetesObsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortiumlinkage disequilibrium score regressionClinical sciencesComorbidityanorexia nervosaLinkage Disequilibriumimmune-related disorderssingle nucleotide polymorphismsCongenitalsystemic lupus erythematosusGWASs2.1 Biological and endogenous factorsneuroticismgenome‐wide associationPediatricbipolar disorderLDSCMental Disordersand Me Research TeamMETASTROKE Consortium of the International Stroke Genetics ConsortiumbioinformaticsPharmacology and Pharmaceutical SciencesSingle NucleotideneuroCHARGE Working GroupBiological SciencesSerious Mental IllnessMental Illnessgenetic correlationC‐reactive proteinCrohn's diseasepsychiatric disordersHereditaryMental HealthImmune System Diseasesobsessive schizophreniaattention deficit‐hyperactivity disorderMental healthFemaleGenetic PhenomenaMedical GeneticsSNPsClinical Sciences610Autoimmune DiseasePolymorphism, Single NucleotidesmokingWhite PeopleC-reactive proteinAutoimmune DiseasesDatabaseschildhood ear infectionHealth Sciences616Behavioral and Social ScienceGeneticsHumansGenetic Predisposition to DiseasePolymorphismFactualtuberculosis susceptibilityInflammation Working Group of the CHARGE Consortiumulcerative colitisPopulation BiologyBiomedical and Clinical SciencesTourette syndromeInflammatory and immune systemHuman GenomeNeurosciencesGenetics and Genomicsattention deficit-hyperactivity disorderallergyBrain Disordersprimary biliary cirrhosisgenome-wide association studiesNetherlands Twin RegistrySchizophreniagenome-wide associationhypothyroidismautoimmune disordermajor depressionceliac diseaseand Neonatal Diseases and AbnormalitiesGenome-Wide Association Studypublication3. Good healthdoi_dedup___PMC6230304303255871983/d5cb79d8-89ed-4be4-b540-66d87a4adb5920.500.11820/a5281c1b-8f9d-498a-a00d-074acc4feb962027.42/14663920.500.14038/4677120.500.14038/29304