Multilocus Heterozygosity and Coronary Heart Disease: Nested Case-Control Studies in Men and Women

Kenneth J. Mukamal, Majken K. Jensen, Tune Hannes Pers, Jennifer K. Pai, Peter Kraft, Eric B. Rimm

    Research output: Contribution to journalJournal articleResearchpeer-review

    401 Downloads (Pure)

    Abstract

    Background: Generalized allelic heterozygosity has been proposed to improve reproductive fitness and has been associated with higher blood pressure, but its association with chronic disease is not well characterized.
    Methods: Using the Affymetrix Genome-Wide Human 6.0 array, we performed whole genome scans in parallel case-control studies of coronary heart disease (CHD) nested in the Health Professionals Follow-up Study and Nurses' Health Study. We examined ∼ 700,000 single nucleotide polymorphisms (SNPs) in 435 men with incident CHD and 878 matched controls and 435 women with incident CHD with 931 matched controls. We examined the relationship of genome-wide heterozygosity with risk of incident of CHD and with baseline levels of cardiovascular risk factors.
    Results: In both cohorts, approximately 227650 (SD 2000) SNPs were heterozygous. The number of heterozygous SNPs was not related to risk of CHD in either men or women (adjusted odds ratios per 2000 heterozygous SNPs 1.01 [95% confidence interval, 0.91-1.13] in women and 0.94 [0.84-1.06] in men). We also found no consistent associations of genome-wide heterozygosity with levels of lipids, inflammatory markers, adhesion molecules, homocysteine, adiponectin, or body-mass index.
    Conclusions: In these parallel nested case-control studies, we found no relationship of multilocus heterozygosity with risk of CHD or its major risk factors. Studies in other populations are needed to rule out associations with lower levels of heterozygosity.
    Original languageEnglish
    Article numbere0124847
    JournalPLOS ONE
    Volume10
    Issue number5
    Number of pages8
    ISSN1932-6203
    DOIs
    Publication statusPublished - 2015

    Bibliographical note

    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

    Keywords

    • Multidisciplinary
    • Quantitative traits
    • Association
    • Malaria
    • Markers
    • Risk

    Fingerprint

    Dive into the research topics of 'Multilocus Heterozygosity and Coronary Heart Disease: Nested Case-Control Studies in Men and Women'. Together they form a unique fingerprint.

    Cite this