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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
  1. X Li (xiali{at}unc.edu)
  1. University of North Carolina at Chapel Hill, United States
    1. K L Monda (monda{at}unc.edu)
    1. University of North Carolina at Chapel Hill, United States
      1. H H H Göring (hgoring{at}sfbrgenetics.org)
      1. Southwest Foundation for Biomedical Research, United States
        1. K Haack (khaack{at}sfbrgenetics.org)
        1. Southwest Foundation for Biomedical Research, United States
          1. S A Cole (scole{at}sfbrgenetics.org)
          1. Southwest Foundation for Biomedical Research, United States
            1. V P Diego (vdiego{at}sfbrgenetics.org)
            1. Southwest Foundation for Biomedical Research, United States
              1. L Almasy (almasy{at}sfbrgenetics.org)
              1. Southwest Foundation for Biomedical Research, United States
                1. S Laston (slaston{at}sfbrgenetics.org)
                1. Southwest Foundation for Biomedical Research, United States
                  1. B V Howard (barbara.v.howard{at}medstar.net)
                  1. MedStar Research Institute, United States
                    1. N M Shara (shara{at}medstar.net)
                    1. MedStar Research Institute, United States
                      1. E T Lee (elisa-lee{at}ouhsc.edu)
                      1. University of Oklahoma, United States
                        1. L G Best (sbest{at}utma.com)
                        1. Missouri Breaks Industries Research, Inc., United States
                          1. R R Fabsitz (fabsitzr{at}nhlbi.nih.gov)
                          1. National Heart, Lung, and Blood Institute, United States
                            1. J W MacCluer (jean{at}sfbrgenetics.org)
                            1. Southwest Foundation for Biomedical Research, United States
                              1. K E North (kari_north{at}unc.edu)
                              1. University of North Carolina at Chapel Hill, United States

                                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.

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