PII-046 - GENOME WIDE ASSOCIATION STUDY (GWAS) OF SECOND-GENERATION ANTIPSYCHOTICS (SGA)-INDUCED METABOLIC SYNDROME (METS) IN BIOME BIOBANK.
Thursday, March 23, 2023
5:00 PM – 6:30 PM EDT
N. El Rouby1, A. Obeng2, M. Preuss2, S. Lee2, R. Nadukuru2, S. Van driest3, M. DelBello1; 1University of Cincinnati, Cincinnati, OH, USA, 2Icahn School of Medicine at Mount Sinai, New York City, NY, USA, 3Vanderbilt Children's Hospital, Nashville, TN, USA.
Assistant Professor University of Cincinnati Cincinnati, Ohio, United States
Background: Second Generation Antipsychotics (SGA) are the mainstay treatment of mental illness disorders, yet challenging to use because of their association with metabolic abnormalities. We aimed to investigate the genetic determinants of SGA-induced Metabolic syndrome (Mets) through a Genome Wide Association Study in BioMe Biobank. Methods: We created a case-control dataset (N=638 controls, 1825 cases) for SGA-induced Mets using electronic health records of patients in BioMe. A case was defined at =>3 months post SGA as a patient who met three out of five criteria of the National Cholesterol Education Program (NCEP): Blood pressure =>130/85 mmHg or antihypertensive use, fasting serum glucose => 100 mg/dL or antidiabetic medication use, serum triglycerides =>150 mg/dL, HDL-cholesterol < 40 mg/dL in men, and < 50 mg/dL in women or antihyperlipidemic use, and body mass index (BMI) =>30. A control was defined as a patient meeting 2 or less criteria. We conducted a GWAS using the Scalable and Accurate Implementation of GEneralized mixed model (SAIGE), stratified by ancestry, and adjusted for age, baseline BMI, baseline diabetes and sex. Ancestry specific GWAS results were meta-analyzed in METAL. Results: We identified three signals that met the genome wide significance on chromosome 16. The rs2170846 (16:85350532 A>G) had the highest association, with the G allele being a risk allele for an increased risk of SGA-Mets (p=1x10-8, z score=5.71, allele frequency=0.36). The rs2170846 SNP is mapped to GSE1 and has been associated with weight, trunk fat mass, whole body free mass in a Phenome Wide Association analysis (PheWAS) in the UK biobank. Conclusion: We identified a new association for SGA-induced Mets on chromosome 16, which needs to be validated. Replication is underway in other data such as UK Biobank and BioVU.
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