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
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 (r2 = 0.38 in whites; r2 = 0.55 in blacks) and PC2 (r2 = 0. 51; r2 = 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 (r2 = 0.38 in whites; r2 = 0.55 in blacks) and PC2 (r2 = 0. 51; r2 = 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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U2 - 10.1210/jc.2003-030553
DO - 10.1210/jc.2003-030553
M3 - Article
C2 - 14671193
AN - SCOPUS:0346101835
SN - 0021-972X
VL - 88
SP - 5935
EP - 5943
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 12
ER -
