Genome-wide linkage scan for plasma high density lipoprotein cholesterol, apolipoprotein A-1 and triglyceride variation among American Indian populations: the Strong Heart Family Study

X Li ¹, K L Monda ¹, H H H Göring ², K Haack ², S A Cole ², V P Diego ², L Almasy ², S Laston ², B V Howard ³, N M Shara ³, E T Lee ⁴, L G Best ⁵, R R Fabsitz ⁶, J W MacCluer ² and K E North ^1*

¹ University of North Carolina at Chapel Hill, United States
² Southwest Foundation for Biomedical Research, United States
³ MedStar Research Institute, United States
⁴ University of Oklahoma, United States
⁵ Missouri Breaks Industries Research, Inc., United States
⁶ National Heart, Lung, and Blood Institute, United States

^* To whom correspondence should be addressed. E-mail: kari_north{at}unc.edu.

Accepted 9 March 2009

Abstract

Background: Recent studies have identified chromosomal regions linked to variation in high density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (Apo A-1) and triglyceride (TG), although results have been inconsistent and previous studies of American Indian populations are limited.

Objective: In an attempt to localize quantitative trait loci (QTLs) influencing HDL-C, Apo A-1 and TG, we conducted genome-wide linkage scans of subjects of the Strong Heart Family Study. Methods: We implemented analyses in 3484 men and women aged 18 years or older, at three study centers.

Results: With adjustment for age, sex and center, we detected a QTL influencing both HDL-C (LOD = 4.4, genome-wide P = 0.001) and Apo A-1 (LOD = 3.2, genome-wide P = 0.020) nearest marker D6S289 at 6p23 in the Arizona sample. Another QTL influencing Apo A-1 was found nearest marker D9S287 at 9q22.2 (LOD = 3.0, genome-wide P = 0.033) in the North and South Dakotas. We detected a QTL influencing TG nearest marker D15S153 at 15q22.31 (LOD = 4.5 in the overall sample and LOD = 3.8 in the Dakotas sample, genome-wide P = 0.0044) and when additionally adjusted for waist, current smoking, current alcohol, current estrogen, lipid treatment, impaired fasting glucose, and diabetes, nearest marker D10S217 at 10q26.2 (LOD = 3.7, genome-wide P = 0.0058) in the Arizona population.

Conclusions: The replication of QTLs in regions of the genome that harbor well-known candidate genes suggest that chromosomes 6p, 9q and 15q warrant further investigation with fine mapping for causative polymorphisms in American Indians.