Identification of female-specific genetic variants for metabolic syndrome and its component traits to improve the prediction of metabolic syndrome in females

BackgroundMetabolic syndrome (MetS), defined as a cluster of metabolic risk factors including dyslipidemia, insulin-resistance, and elevated blood pressure, has been known as partly heritable. MetS effects the lives of many people worldwide, yet females have been reported to be more vulnerable to this cluster of risks.MethodsTo elucidate genetic variants underlying MetS specifically in females, we performed a genome-wide association study (GWAS) for MetS as well as its component traits in a total of 9932 Korean female subjects (including 2276 MetS cases and 1692 controls). To facilitate the prediction of MetS in females, we calculated a genetic risk score (GRS) combining 14 SNPs detected in our GWA analyses specific for MetS.ResultsGWA analyses identified 14 moderate signals (P-meta<5X10(-5)) specific to females for MetS. In addition, two genome-wide significant female-specific associations (P-meta<5X10(-8)) were detected for rs455489 in DSCAM for fasting plasma glucose (FPG) and for rs7115583 in SIK3 for high-density lipoprotein cholesterol (HDLC). Logistic regression analyses (adjusted for area and age) between the GRS and MetS in females indicated that the GRS was associated with increased prevalence of MetS in females (P=5.28x10(-14)), but not in males (P=3.27x10(-1)). Furthermore, in the MetS prediction models using GRS, the area under the curve (AUC) of the receiver operating characteristics (ROC) curve was higher in females (AUC=0.85) than in males (AUC=0.57).ConclusionThis study highlights new female-specific genetic variants associated with MetS and its component traits and suggests that the GRS of MetS variants is a likely useful predictor of MetS in females.