TY - JOUR

T1 - Genome-wide linkage scan for the metabolic syndrome in the HERITAGE Family Study

AU - Loos, Ruth J F

AU - Katzmarzyk, Peter T

AU - Rao, D C

AU - Rice, Treva

AU - Leon, Arthur S

AU - Skinner, James S

AU - Wilmore, Jack H

AU - Rankinen, Tuomo

AU - Bouchard, Claude

AU - HERITAGE Family Study

PY - 2003/12

Y1 - 2003/12

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - African Continental Ancestry Group/genetics

KW - Analysis of Variance

KW - Chromosome Mapping

KW - European Continental Ancestry Group/genetics

KW - Female

KW - Genetic Linkage

KW - Genome, Human

KW - Humans

KW - Male

KW - Metabolic Syndrome/genetics

KW - Middle Aged

KW - Phenotype

KW - Principal Component Analysis

KW - Quantitative Trait Loci

U2 - 10.1210/jc.2003-030553

DO - 10.1210/jc.2003-030553

M3 - Journal article

C2 - 14671193

VL - 88

SP - 5935

EP - 5943

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -