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Admixture mapping of ankle–arm index: identification of a candidate locus associated with peripheral arterial disease
  1. M L Scherer1,
  2. M A Nalls2,
  3. L Pawlikowska3,4,
  4. E Ziv3,4,
  5. G Mitchell5,
  6. S Huntsman3,6,
  7. D Hu3,6,
  8. K Sutton-Tyrrell7,
  9. E G Lakatta8,
  10. W-C Hsueh3,
  11. A B Newman7,9,
  12. A Tandon10,11,
  13. L Kim1,
  14. P-Y Kwok3,4,12,
  15. A Sung3,4,
  16. R Li13,
  17. B Psaty14,
  18. A P Reiner14,
  19. T Harris1
  1. 1Laboratory of Epidemiology, Demography and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA
  2. 2Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA
  3. 3Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA
  4. 4Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA
  5. 5Cardiovascular Engineering, Inc, Waltham, Massachusetts, USA
  6. 6Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
  7. 7Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  8. 8Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland, USA
  9. 9Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  10. 10Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
  11. 11Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
  12. 12Department of Dermatology, University of California, San Francisco, San Francisco, California, USA
  13. 13University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
  14. 14School of Public Health and Community Medicine, Cardiovascular Health Research Unit University of Washington, Seattle, Washington, USA
  1. Correspondence to Dr T B Harris, Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Gateway Building, Suite 3C-309, 7201 Wisconsin Ave, MSC 9205, Bethesda, MD 20892-9205, USA; harris99{at}nia.nih.gov

Abstract

Background Peripheral arterial disease (PAD) is associated with significant morbidity and mortality, and has a higher prevalence in African Americans than Caucasians. Ankle–arm index (AAI) is the ratio of systolic blood pressure in the leg to that in the arm, and, when low, is a marker of PAD.

Methods The authors used an admixture mapping approach to search for genetic loci associated with low AAI. Using data from 1040 African American participants in the observational, population based Health, Aging, and Body Composition Study who were genotyped at 1322 single nucleotide polymorphisms (SNPs) that are informative for African versus European ancestry and span the entire genome, we estimated genetic ancestry in each chromosomal region and then tested the association between AAI and genetic ancestry at each locus.

Results The authors found a region of chromosome 11 that reaches its peak between 80 and 82 Mb associated with low AAI (p<0.001 for rs12289502 and rs9665943, both within this region). 753 African American participants in the observational, population based Cardiovascular Health Study were genotyped at rs9665943 to test the reproducibility of this association, and this association was also statistically significant (odds ratio (OR) for homozygous African genotype 1.59, 95% confidence interval (CI) 1.12 to 2.27). Another candidate SNP (rs1042602) in the same genomic region was tested in both populations, and was also found to be significantly associated with low AAI in both populations (OR for homozygous African genotype 1.89, 95% CI 1.29 to 2.76).

Conclusion This study identifies a novel region of chromosome 11 representing an area with a potential candidate gene associated with PAD in African Americans.

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Footnotes

  • MLS and MAN contributed equally as first authors to this manuscript

  • Funding The research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant number U01 HL080295 from the National Heart, Lung, and Blood Institute, as well as the Intramural Research Program of the National Institute on Aging, contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 with additional contribution from the National Institute of Neurological Disorders and Stroke. DR was supported by a Burroughs Wellcome Career Development Award in the Biomedical Sciences. EZ's effort was supported by a career development award from the NCI (K22 CA109351), the Department of Defense Breast Cancer Research Program (BC030551), and the NIH/NIA (U19 AG23122). A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm.

  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and Peer review Not commissioned; externally peer reviewed.

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