Genome-wide linkage scans for loci affecting total cholesterol, HDL-C, and triglycerides: the Family Blood Pressure Program.
Atherosclerosis accounts for 75% of all deaths from cardiovascular disease and includes coronary heart disease (CHD), stroke, and other diseases of the arteries. More than half of all CHD is attributable to abnormalities in levels and metabolism of lipids. To locate genes that affect total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglycerides, genome-wide linkage scans for quantitative trait loci were performed using variance components methods as implemented in SOLAR on a large diverse sample recruited as part of the Family Blood Pressure Program. Phenotype and genetic marker data were available for 9,299 subjects in 2,953 families for total cholesterol, 8,668 subjects in 2,736 families for HDL, and 7,760 subjects in 2,499 families for triglycerides. Mean lipid levels were adjusted for the effects of sex, age, age2, age-by-sex interaction, body mass index, smoking status, and field center. HDL-C and triglycerides were further adjusted for average total alcoholic drinks per week and estrogen use. Significant linkage was found for total cholesterol on chromosome 2 (LOD=3.1 at 43 cM) in Hispanics and for HDL-C on chromosome 3 (LOD=3.0 at 182 cM) and 12 (LOD=3.5 at 124 cM) in Asians. In addition, there were 13 regions that showed suggestive linkage (LOD >or= 2.0); 7 for total cholesterol, 4 for HDL, and 2 for triglycerides. The identification of these loci affecting lipid phenotypes and the apparent congruence with previous linkage results provides increased support that these regions contain genes influencing lipid levels.
Bielinski
Suzette J
SJ
University of Minnesota, Division of Epidemiology and Community Health, West Bank Office Building Suite 300, 1300 South 2nd Street, Minneapolis, MN 55454, USA. Bielinski@epi.umn.edu
Tang
Weihong
W
Pankow
James S
JS
Miller
Michael B
MB
Mosley
Thomas H
TH
Boerwinkle
Eric
E
Olshen
Richard A
RA
Curb
J David
JD
Jaquish
Cashell E
CE
Rao
D C
DC
Weder
Alan
A
Arnett
Donna K
DK
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000235:genetics; D002784:Cholesterol / Q000097:blood* / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D005190:Family; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D040641:Quantitative Trait Loci; D014280:Triglycerides / Q000097:blood* / Q000235:genetics
D008076:Cholesterol, HDL; D014280:Triglycerides; D002784:Cholesterol