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Papers In Press, published online ahead of print March 1, 2004
J. Lipid Res., doi:10.1194/jlr.M300401-JLR200

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Journal of Lipid Research, Vol. 45, 419-426, March 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Genome-wide linkage scan reveals multiple susceptibility loci influencing lipid and lipoprotein levels in the Québec Family Study

Y. Bossé^*,, Y. C. Chagnon, J-P. Després^*,,**, T. Rice, D. C. Rao, C. Bouchard, L. Pérusse^*** and M-C. Vohl^1,*,

^* Lipid Research Center, Laval University Medical Research Center, Québec, Canada
Department of Food Science and Nutrition, Laval University, Québec, Canada
Laval University-Robert Giffard Research Center, Beauport, Canada
^** The Quebec Heart Institute, Québec, Canada
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO
Pennington Biomedical Research Center, Baton Rouge, LA
^*** Division of Kinesiology, Department of Social and Preventive Medicine, Laval University, Québec, Canada

¹ To whom correspondence should be addressed. e-mail: marie-claude.vohl{at}crchul.ulaval.ca

A genome-wide linkage study was performed to identify chromosomal regions harboring genes influencing lipid and lipoprotein levels. Linkage analyses were conducted for four quantitative lipoprotein/lipid traits, i.e., total cholesterol, triglyceride, HDL-cholesterol (HDL-C), and LDL-C concentrations, in 930 subjects enrolled in the Québec Family Study. A maximum of 534 pairs of siblings from 292 nuclear families were available. Linkage was tested using both allele-sharing and variance-component linkage methods. The strongest evidence of linkage was found on chromosome 12q14.1 at marker D12S334 for HDL-C, with a logarithm of the odds (LOD) score of 4.06. Chromosomal regions harboring quantitative trait loci (QTLs) for LDL-C included 1q43 (LOD = 2.50), 11q23.2 (LOD = 3.22), 15q26.1 (LOD = 3.11), and 19q13.32 (LOD = 3.59). In the case of triglycerides, three markers located on 2p14, 11p13, and 11q24.1 provided suggestive evidence of linkage (LOD > 1.75). Tests for total cholesterol levels yielded significant evidence of linkage at 15q26.1 and 18q22.3 with the allele-sharing linkage method, but the results were nonsignificant with the variance-component method.

In conclusion, this genome scan provides evidence for several QTLs influencing lipid and lipoprotein levels. Promising candidate genes were located in the vicinity of the genomic regions showing evidence of linkage.

Abbreviations: apoA-I, apolipoprotein A-I; BMI, body mass index; FCHL, familial combined hyperlipidemia; IBD, identical by descent; LOD, logarithm of the odds; QTL, quantitative trait locus

Supplementary key words genome scan • genetics • blood lipids • quantitative trait locus • triglyceride • cholesterol

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