Linkage analysis of LDL cholesterol in American Indian populations: the Strong Heart Family Studys⃞

K.E. North; H.H.H. Göring; S.A. Cole; V.P. Diego; L. Almasy; S. Laston; T. Cantu; B.V. Howard; E.T. Lee; L.G. Best; R.R. Fabsitz; J.W. MacCluer

Journal of Lipid Research (Jan 2006)

Linkage analysis of LDL cholesterol in American Indian populations: the Strong Heart Family Studys⃞

K.E. North,
H.H.H. Göring,
S.A. Cole,
V.P. Diego,
L. Almasy,
S. Laston,
T. Cantu,
B.V. Howard,
E.T. Lee,
L.G. Best,
R.R. Fabsitz,
J.W. MacCluer

Affiliations

K.E. North: Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX; MedStar Research Institute, Washington, DC; Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Missouri Breaks Industries Research, Inc., Timber Lake, SD; Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, MD
H.H.H. Göring: Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX; MedStar Research Institute, Washington, DC; Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Missouri Breaks Industries Research, Inc., Timber Lake, SD; Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, MD
S.A. Cole: Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX; MedStar Research Institute, Washington, DC; Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Missouri Breaks Industries Research, Inc., Timber Lake, SD; Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, MD
V.P. Diego: Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX; MedStar Research Institute, Washington, DC; Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Missouri Breaks Industries Research, Inc., Timber Lake, SD; Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, MD
L. Almasy: Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX; MedStar Research Institute, Washington, DC; Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Missouri Breaks Industries Research, Inc., Timber Lake, SD; Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, MD
S. Laston: Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX; MedStar Research Institute, Washington, DC; Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Missouri Breaks Industries Research, Inc., Timber Lake, SD; Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, MD
T. Cantu: Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX; MedStar Research Institute, Washington, DC; Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Missouri Breaks Industries Research, Inc., Timber Lake, SD; Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, MD
B.V. Howard: Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX; MedStar Research Institute, Washington, DC; Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Missouri Breaks Industries Research, Inc., Timber Lake, SD; Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, MD
E.T. Lee: Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX; MedStar Research Institute, Washington, DC; Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Missouri Breaks Industries Research, Inc., Timber Lake, SD; Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, MD
L.G. Best: Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX; MedStar Research Institute, Washington, DC; Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Missouri Breaks Industries Research, Inc., Timber Lake, SD; Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, MD
R.R. Fabsitz: Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX; MedStar Research Institute, Washington, DC; Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Missouri Breaks Industries Research, Inc., Timber Lake, SD; Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, MD
J.W. MacCluer: Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX; MedStar Research Institute, Washington, DC; Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Missouri Breaks Industries Research, Inc., Timber Lake, SD; Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, MD

Journal volume & issue: Vol. 47, no. 1
pp. 59 – 66

Abstract

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Previous studies have demonstrated that low density lipoprotein cholesterol (LDL-C) concentration is influenced by both genes and environment. Although rare genetic variants associated with Mendelian causes of increased LDL-C are known, only one common genetic variant has been identified, the apolipoprotein E gene (APOE). In an attempt to localize quantitative trait loci (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 years 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 [logarithm of odds (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 an association was detected with the APOE*ϵ2 and APOE*ϵ4 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.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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