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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 Li1,
  2. K L Monda1,
  3. H H H Göring2,
  4. K Haack2,
  5. S A Cole2,
  6. V P Diego2,
  7. L Almasy2,
  8. S Laston2,
  9. B V Howard3,
  10. N M Shara3,
  11. E T Lee4,
  12. L G Best5,
  13. R R Fabsitz6,
  14. J W MacCluer2,
  15. Kari E North1,7
  1. 1
    Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
  2. 2
    Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas, USA
  3. 3
    MedStar Research Institute, Washington, DC, USA
  4. 4
    Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
  5. 5
    Missouri Breaks Industries Research, Inc., Timber Lake, South Dakota, USA
  6. 6
    Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute Bethesda, Maryland, USA
  7. 7
    Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina, USA
  1. Dr K North, Department of Epidemiology and Carolina Center for Genome Sciences, University of North Carolina Chapel Hill, 137 E Franklin Street, Suite 306, Chapel Hill, NC 27514, USA; kari_north{at}unc.edu

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.

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Footnotes

  • Additional tables are published online only at http://jmg.bmj.com/content/vol46/issue7

  • Funding: This research was funded by a cooperative agreement that includes grants U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, and U01 HL65521 from the National Heart, Lung, and Blood Institute. We would also like to acknowledge US Public Health Service grant MH059490 from the National Institutes of Health. This investigation was conducted in facilities constructed with support from Research Facilities Improvement Program Grants C06 RR13556 and C06 RR017515 from the National Center for Research Resources, National Institutes of Health.

  • Competing interests: None declared.

  • Patient consent: Obtained.

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