Genome-wide linkage scan for the metabolic syndrome: the GENNID study

In the United States, the metabolic syndrome (MetS) constitutes a major public health problem with over 47 million persons meeting clinical criteria for MetS. Numerous studies have suggested genetic susceptibility to MetS. The goals of this study were (i) to identify susceptibility loci for MetS in well-characterized families with type 2 diabetes (T2D) in four ethnic groups and (ii) to determine whether evidence for linkage varies across the four groups. The GENNID study (Genetics of NIDDM) is a multicenter study established by the American Diabetes Association in 1993 and comprises a comprehensive, well-characterized resource of T2D families from four ethnic groups (whites, Mexican Americans, African Americans, and Japanese Americans). Principal component factor analysis (PCFA) was used to define quantitative phenotypes of the MetS. Variance components linkage analysis was conducted using microsatellite markers from a 10-cM genome-wide linkage scan, separately in each of the four ethnic groups. Three quantitative MetS factors were identified by PCFA and used as phenotypes for MetS: (i) a weight/waist factor, (ii) a blood pressure factor, and (iii) a lipid factor. Evidence for linkage to each of these factors was observed. For each ethnic group, our results suggest that several regions harbor susceptibility genes for the MetS. The strongest evidence for linkage for MetS phenotypes was observed on chromosome 2 (2q12.1-2q13) in the white sample and on chromosome 3 (3q26.1-3q29) in the Mexican-American sample. In conclusion, the results suggest that several regions harbor MetS susceptibility genes and that heterogeneity may exist across groups.