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A more recent version of this article appeared on January 1, 2006

Papers In Press, published online ahead of print November 1, 2005
J. Lipid Res., doi:10.1194/jlr.M500395-JLR200
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Submitted on September 1, 2005
Revised on October 31, 2005
Accepted on October 31, 2005

Linkage analysis of LDL cholesterol in American Indian populations: The strong heart family study

Kari E. North, Harald H. H. Göring, Shelley A. Cole, Vincent P. Diego, Laura Almasy, Sandra Laston, Teresa Cantu, Barbara V. Howard, Elisa T. Lee, Lyle G. Best, Richard R. Fabsitz, and Jean W. MacCluer

Epidemiology Dept., UNC Chapel Hill, Chapel Hill, NC 27587

Corresponding Author: kari_north{at}unc.edu

Previous studies have demonstrated that low density lipoprotein cholesterol (LDL-C) concentration is influenced by both genes and environment. While rare genetic variants associated with Mendelian causes of elevated LDL-C are known, only one common genetic variant has been identified, APOE. In an attempt to localize QTLs influencing LDL-C, we conducted a genome-wide linkage scan of LDL-C in participants of the Strong Heart Family Study (SHFS). Nine hundred eighty men and women, age 18 or older, in 32 extended families at three centers (in Arizona, Oklahoma, and North and South Dakota) were phenotyped for LDL-C concentration and other risk factors. Using a variance component approach and the program SOLAR, and after accounting for the effects of covariates, we detected a QTL influencing LDL-C on chromosome 19 nearest marker D19S888 at 19q13.41 (LOD = 4.3) in the sample from the Dakotas. This region on chromosome 19 includes many possible candidate genes including the APOE/C1/C4/C2 gene cluster. In follow-up association analyses, no significant evidence for association was detected with the APOE*e2 and *e4 alleles (P = 0.76 and P = 0.53, respectively). Suggestive evidence of linkage to LDL-C was detected on chromosomes 3q, 4q, 7p, 9q, 10p, 14q, and 17q. These linkage signals overlap positive findings for lipid-related traits and harbor plausible candidate genes for LDL-C.


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