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Linkage mapping of CVD risk traits in the isolated Norfolk Island population

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Abstract

To understand the underlying genetic architecture of cardiovascular disease (CVD) risk traits, we undertook a genome-wide linkage scan to identify CVD quantitative trait loci (QTLs) in 377 individuals from the Norfolk Island population. The central aim of this research focused on the utilization of a genetically and geographically isolated population of individuals from Norfolk Island for the purposes of variance component linkage analysis to identify QTLs involved in CVD risk traits. Substantial evidence supports the involvement of traits such as systolic and diastolic blood pressures, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, body mass index and triglycerides as important risk factors for CVD pathogenesis. In addition to the environmental influences of poor diet, reduced physical activity, increasing age, cigarette smoking and alcohol consumption, many studies have illustrated a strong involvement of genetic components in the CVD phenotype through family and twin studies. We undertook a genome scan using 400 markers spaced approximately 10 cM in 600 individuals from Norfolk Island. Genotype data was analyzed using the variance components methods of SOLAR. Our results gave a peak LOD score of 2.01 localizing to chromosome 1p36 for systolic blood pressure and replicated previously implicated loci for other CVD relevant QTLs.

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Abbreviations

BMI:

Body mass index

cM:

Centimorgan

CVD:

Cardiovascular disease

IBD:

Identity-by-descent

DBP:

Diastolic blood pressure

HDL-C:

High-density lipoprotein-cholesterol

LOD:

Logarithm of the odds ratio

LDL-C:

Low-density lipoprotein-cholesterol

QTL:

Quantitative trait loci

SBP:

Systolic blood pressure

TC:

Total cholesterol

TG:

Triglyceride

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Acknowledgments

An Australian National Health and Medical Research Council (NHMRC) Medical Genomics, Bioinformatics and Proteomics Program (MGBPP) grant plus an Australian National Heart Foundation (NHF) grant supported this research. The SOLAR statistical genetics computer package is supported by a grant from the US National Institute of Mental Health (MH059490). The supercomputing facilities used for this work at the AT&T Genetics Computing enter were supported in part by a gift from the AT&T Foundation. We would like to acknowledge the help of Paul Jardine and the Research Computing Services team at Griffith University for providing support on Griffth’s Sun Solaris HPC cluster as well as Dr Peter Visscher (QIMR) for providing manuscript advice. We appreciate the comments by the two reviewers of this manuscript. Lastly, this study would not have commenced without the participation if Norfolk Island population, we thank them for their involvement in this and future research.

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Authors and Affiliations

  1. Genomics Research Centre, Griffith Institute for Health and Medical Research, Griffith University, Gold Coast PMB 50, GCMC Bundall 9726, Gold Coast, Australia

    C. Bellis, H. C. Cox, S. Quinlan, R. A. Lea & L. R. Griffiths

  2. Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, 78227, USA

    C. Bellis, T. D. Dyer, J. C. Charlesworth & J. Blangero

  3. Division of Information Services, Griffith University, Gold Coast, Australia

    K. N. Begley

  4. Institute of Environmental Science and Research Ltd, Porirua, New Zealand

    R. A. Lea

  5. Centre National de Génotypage, 2 Rue Gaston Cremieux, Evry, France

    S. C. Heath

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  1. C. Bellis
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  2. H. C. Cox
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  3. T. D. Dyer
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  6. S. Quinlan
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  9. J. Blangero
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  10. L. R. Griffiths
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Correspondence to L. R. Griffiths.

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Bellis, C., Cox, H.C., Dyer, T.D. et al. Linkage mapping of CVD risk traits in the isolated Norfolk Island population. Hum Genet 124, 543–552 (2008). https://doi.org/10.1007/s00439-008-0580-y

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  • DOI: https://doi.org/10.1007/s00439-008-0580-y

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