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• W4387476715 abstract "Externalizing (EXT) refers to a group of psychiatric disorders and behaviors related to self-regulation, such as substance use disorders, aggression, and antisocial behaviors. Externalizing behaviors often vary by sex (male/female) and co-occur with health-related outcomes. These associations may reflect common genetic factors that influence both externalizing behavior and other health-related outcomes. Using electronic health records (EHR) obtained from a US-based biobank from the Vanderbilt University Medical Center biorepository (BioVU; N = 72,225), we performed a phenome-wide association study (PheWAS) to assess the sex-stratified associations between a polygenic scores (PGS) for EXT and 1,817 clinical EHR-based diagnoses. The sex-stratified PGS for EXT was based on the latest EXT genome-wide association study (N = 1,492,085). We first prioritized phenotypes with a main effect in at least one sex (i.e., male or female) and then returned to the sex-combined analysis to test whether there were significant differences in the odds ratios between males and females by performing an interaction test (Sex*PGS). We identified 418 medical conditions associated with PGS-EXT (FDR 5%); 154 traits were associated in both males and females; 172 and 92 traits were associated in only females or males respectively. The sex‐combined EXT PGS interaction analysis revealed 9 FDR p < 0.01 significant interactions. Traits such as HIV (males: B = 0.33, p = 1.97E-15; females: B = 0.54, p = 2.25E-08), alcohol-related disorders (males: B = 0.33, p = 3.16E-24; females: B = 0.40, p = 9.85E-17), and viral hepatitis (males: B = 0.36, p = 4.39E-26; females: B = 0.44, p = 4.63E-22) were more strongly associated with the EXT PGS in males, whereas traits pertaining to cardiovascular health, such as ischemic heart disease (males: B = 0.08, p = 1.87E-07; females: B = 0.15, p = 4.23E-16) and coronary atherosclerosis (males: B = 0.08, p = 1.36E-06; females: B = 0.14, p = 7.85E-13), were more strongly associated in females. Overall our findings indicate a sex-specific increased risk of medical conditions in individuals with high genetic liability for EXT. The effect sizes for the substance use and infectious disease traits were greater in males, while the effect sizes for cardiovascular conditions were greater in females, indicating that males and females may be particularly vulnerable to these specific conditions. These results highlight the benefits of sex-specific PheWAS of externalizing symptoms and other behavioral and somatic traits." @default.
• W4387476715 created "2023-10-11" @default.
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• W4387476715 date "2023-10-01" @default.
• W4387476715 modified "2023-10-16" @default.
• W4387476715 title "W98. A PHENOME-WIDE ASSOCIATION STUDY OF POLYGENIC LIABILITY FOR EXTERNALIZING IN A EUROPEAN COHORT REVEALS SEX-SPECIFIC ASSOCIATIONS WITH NUMEROUS MEDICAL OUTCOMES" @default.
• W4387476715 doi "https://doi.org/10.1016/j.euroneuro.2023.08.284" @default.
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