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Admixture mapping of ankle-arm index: identification of a candidate locus associated with peripheral arterial disease
  1. Matthew L Scherer (matt.l.scherer{at}gmail.com)
  1. Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, United States
    1. Michael A Nalls (nallsm{at}mail.nih.gov)
    1. Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, United States
      1. Ludmila Pawlikowska (pawlikowskal{at}anesthesia.ucsf.edu)
      1. Institute for Human Genetics, University of California, San Francisco, United States
        1. Elad Ziv (elad.ziv{at}ucsf.edu)
        1. Institute for Human Genetics, University of California, San Francisco, United States
          1. Gary F Mitchell (garyfmitchell{at}mindspring.com)
          1. Cardiovascular Engineering, Inc, United States
            1. Scott Huntsman
            1. Institute for Human Genetics, University of California, San Francisco, United States
              1. Donglei Hu
              1. University of California, San Francisco, United States
                1. Kim Sutton-Tyrrell (tyrrell{at}edc.pitt.edu)
                1. Graduate School of Public Health, University of Pittsburgh, United States
                  1. Edward G Lakatta
                  1. Laboratory of Cardiovascular Science, National Institute on Aging, United States
                    1. Wen-Chi Hsueh
                    1. Institute for Human Genetics, University of California, San Francisco, United States
                      1. Anne B Newman (newmana{at}edc.pitt.edu)
                      1. University of Pittsburgh, United States
                        1. Arti Tandon (atandon{at}broad.mit.edu)
                        1. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, United States
                          1. Lauren Kim
                          1. Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, United States
                            1. Pui-Yan Kwok (pui.kwok{at}ucsf.edu)
                            1. Institute for Human Genetics, University of California, San Francisco, United States
                              1. Andrew Sung (andrew.sung{at}ucsf.edu)
                              1. Institute for Human Genetics, University of California, San Francisco, United States
                                1. RongLing Li (rli2{at}utmem.edu)
                                1. University of Tennessee Health Sciences Center, United States
                                  1. Bruce Psaty
                                  1. University of Washington, United States
                                    1. Alex P Reiner (apreiner{at}u.washington.edu)
                                    1. University of Washington, United States
                                      1. Tamara B Harris (harris99{at}mail.nih.gov)
                                      1. Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, United States

                                        Abstract

                                        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. We 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. We 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) 1.12-2.27)). 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 1.29-2.76)). 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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