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

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 localise 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 centres.

Results: With adjustment for age, sex and centre, we detected a QTL influencing both HDL-C (logarithm of odds (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 oestrogen, 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 harbour well known candidate genes suggest that chromosomes 6p, 9q and 15q warrant further investigation with fine mapping for causative polymorphisms in American Indians.

Figure 1

Multipoint LOD scores on chromosome 6 for HDL cholesterol. Results for combined and stratified analyses shown. Model 1 was adjusted for age, sex, and field center (combined analysis). Model 2 was additionally adjusted for waist circumference, current smoking status, current alcohol consumption, current estrogen use, lipid treatment status, impaired fasting glucose and diabetes status. AZ, Arizona field center; DA, Dakotas field centers; OK, Oklahoma field center; cM, Haldane centimorgans.

Figure 2

Multipoint LOD scores on chromosome 6 for apolipoprotein A-I. Results for combined and stratified analyses shown. Model 1 was adjusted for age, sex, and field center (combined analysis). Model 2 was additionally adjusted for waist circumference, current smoking status, current alcohol consumption, current estrogen use, lipid treatment status, impaired fasting glucose and diabetes status. AZ, Arizona field center; DA, Dakotas field centers; OK, Oklahoma field center; cM, Haldane centimorgans.

Figure 3

Multipoint LOD scores on chromosome 9 for apolipoprotein A-I. Results for combined and stratified analyses shown. Model 1 was adjusted for age, sex, and field center (combined analysis). Model 2 was additionally adjusted for waist circumference, current smoking status, current alcohol consumption, current estrogen use, lipid treatment status, impaired fasting glucose and diabetes status. AZ, Arizona field center; DA, Dakotas field centers; OK, Oklahoma field center; cM, Haldane centimorgans.

Figure 4

Multipoint adjusted LOD scores on chromosome 15 for triglycerides. Results for combined and stratified analyses shown. Model 1 was adjusted for age, sex, and field center (combined analysis). Model 2 was additionally adjusted for waist circumference, current smoking status, current alcohol consumption, current estrogen use, lipid treatment status, impaired fasting glucose and diabetes status. AZ, Arizona field center; DA, Dakotas field centers; OK, Oklahoma field center; cM, Haldane centimorgans.

Figure 5

Multipoint adjusted LOD scores on chromosome 10 for triglycerides. Results for combined and stratified analyses shown. Model 1 was adjusted for age, sex, and field center (combined analysis). Model 2 was additionally adjusted for waist circumference, current smoking status, current alcohol consumption, current estrogen use, lipid treatment status, impaired fasting glucose and diabetes status. AZ, Arizona field center; DA, Dakotas field centers; OK, Oklahoma field center; cM, Haldane centimorgans.