Genetic epidemiology of Syndrome X disorders on Kosrae. D. Shmulewitz1, S.C. Heath1, S.B. Auerbach2, M.L. Blundell1, J.D. Winick1, S. Signorini1, J.L. Breslow1, J. Ott1, T. Lehner1, M. Stoffel1, J.M. Friedman1. 1) Starr Center for Human Genetics, The Rockefeller University, New York, NY; 2) Health Resources and Services Administration, Department of Health and Human Services, New York, NY.
Syndrome X, a term used for the observed clustering of metabolic disorders, includes obesity, type II diabetes, hypertension, and dyslipidemia/heart disease. These disorders have been shown to have underlying complex genetic inheritance. We studied the prevalence and genetic epidemiology of these disorders on the Pacific island of Kosrae. This population based study included 2188 individuals (>90% of the adults on the island), of whom 1709 have been placed on a single pedigree. Participants in the study answered questions on their health status, family relationships, demographics and socioeconomic status. Subjects also underwent a clinical evaluation that included: anthropometric measures(weight, height, waist, hip), serum chemistries (leptin, fasting blood sugar [FBS], insulin, total cholesterol [TC], triglycerides [TG], apolipoproteins A1 [ApoA1] and B [ApoB]) and blood pressure (BP) measurements. Statistical analyses were carried out with the SAS package, and heritability and segregation analyses were performed using MORGAN and LOKI. The population on Kosrae showed, relative to the US, an increased prevalence of obesity (BMI>=35, 24%), diabetes (FBS>=126, 12%), hypertension (systolic BP>=140 or diastolic BP>=90, 17%), and dyslipidemia (TC>=240 or TG>=200 or ApoA1£88 or ApoB>=120, 20%). After adjusting for the covariates, sex, age, smoking, village of residence, and parity, heritabilities for the traits were calculated. They ranged from 0.20-0.64, indicating a significant genetic component for all. Segregation analyses showed significant evidence for multiple quantitative trait loci (QTL) for all the variables. Examples of major gene effects include BMI (25% of variance), FBS (51%), TC (41%), and BP (38%). This population is uniquely suited for further gene-mapping experiments, to find genes that are involved in the development of obesity, diabetes, hypertension, dyslipidemia, and their clustering in Syndrome X.