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Admixture mapping for hypertension loci with genome-scan markers

Nature Genetics volume 37, pages 177–181 (2005)Cite this article

Abstract

Identification of genetic variants that contribute to risk of hypertension is challenging. As a complement to linkage and candidate gene association studies, we carried out admixture mapping using genome-scan microsatellite markers among the African American participants in the US National Heart, Lung, and Blood Institute's Family Blood Pressure Program. This population was assumed to have experienced recent admixture from ancestral groups originating in Africa and Europe. We used a set of unrelated individuals from Nigeria to represent the African ancestral population and used the European Americans in the Family Blood Pressure Program to provide estimates of allele frequencies for the European ancestors. We genotyped a common set of 269 microsatellite markers in the three groups at the same laboratory. The distribution of marker location–specific African ancestry, based on multipoint analysis, was shifted upward in hypertensive cases versus normotensive controls, consistent with linkage to genes conferring susceptibility. This shift was largely due to a small number of loci, including five adjacent markers on chromosome 6q and two on chromosome 21q. These results suggest that chromosome 6q24 and 21q21 may contain genes influencing risk of hypertension in African Americans.

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Figure 1: Distribution of δ values and excess African ancestry.
Figure 2: Genome-wide marker information content and distributions of Z scores.

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Acknowledgements

We thank D. Kan for his assistance in programming. This work was supported by grants awarded to the Family Blood Pressure Program, which is supported by a series of cooperative agreements from the National Heart, Lung and Blood Institute to GenNet, HyperGEN, GENOA and SAPPHIRe. The work was also supported by the Reynolds Cardiovascular Clinical Research Center at the University of Texas Southwestern, Dallas, Texas, USA. Genotype data for the Nigerian samples are available on request from R.S.C. (rcooper@lumc.edu).

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Authors and Affiliations

  1. Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, 2160 S. First Ave., Maywood, 60153, Illinois, USA

    Xiaofeng Zhu, Amy Luke & Richard S Cooper

  2. Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA

    Tom Quertermous

  3. Department of Genetics, University of Texas, Houston, Texas, USA

    Craig Hanis

  4. Department of Medicine (Geriatrics), University of Mississippi Medical Center, Jackson, Mississippi, USA

    Tom Mosley

  5. Division of Biostatistics, Washington University, St. Louis, Missouri, USA

    C Charles Gu & Dabeeru C Rao

  6. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Hua Tang

  7. Department of Genetics, Stanford University School of Medicine, Stanford, 94305-5120, California, USA

    Neil Risch

  8. Division of Research, Kaiser Permanente, Oakland, California, USA

    Neil Risch

  9. Department of Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA

    Alan Weder

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Corresponding author

Correspondence to Neil Risch.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Results of logistic regression of hypertension on marker location-specific African ancestry after adjusting for sex, age and body mass index. (PDF 86 kb)

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Zhu, X., Luke, A., Cooper, R. et al. Admixture mapping for hypertension loci with genome-scan markers. Nat Genet 37, 177–181 (2005). https://doi.org/10.1038/ng1510

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