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      Genome-wide linkage scan for the metabolic syndrome in the HERITAGE Family Study.

      The Journal of Clinical Endocrinology and Metabolism

      Adolescent, Adult, African Continental Ancestry Group, genetics, Analysis of Variance, Chromosome Mapping, European Continental Ancestry Group, Female, Genetic Linkage, Genome, Human, Humans, Male, Metabolic Syndrome X, Middle Aged, Phenotype, Principal Component Analysis, Quantitative Trait Loci

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          The metabolic syndrome involves multiple and interactive effects of genes and environmental factors. To identify chromosomal regions encoding genes possibly predisposing to the metabolic syndrome, we performed a genome-wide scan with 456 white and 217 black participants from 204 nuclear families of the HERITAGE Family Study, using regression-based, single- and multipoint linkage analyses on 509 markers. A principal component analysis was performed on 7 metabolic syndrome-related phenotypes. Two principal components, PC1 and PC2 (55% of the variance), were used as metabolic syndrome phenotypes. ANOVA was used to quantify the familial aggregation of PC1 and PC2. Family membership contributed significantly (P < 0.0023) to the variance in PC1 (r(2) = 0.38 in whites; r(2) = 0.55 in blacks) and PC2 (r(2) = 0.51; r(2) = 0.48). In whites, promising evidence for linkage (P < 0.0023) was found for PC1 (2 markers on 10p11.2) and PC2 (a marker on 19q13.4). Suggestive evidence of linkage (0.01 > P > 0.0023) appeared for PC1 (1q41 and 9p13.1) and PC2 (2p22.3). In blacks, promising linkage was found for PC2 on 1p34.1, and suggestive linkage was found on 7q31.3 and 9q21.1. The genome-wide scan revealed evidence for quantitative trait loci on chromosomal regions that have been previously linked with individual cardiovascular disease and type 2 diabetes risk factors. Some of these chromosomal regions harbor promising potential candidate genes.

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