Address of Corresponding Author

Hum Hered 2004;57:142-155 (DOI: 10.1159/000079245)

  Key Words

• Genetic association studies
• Population subdivision
• Stratification
• Y chromosome
• Autosomal SNPs
• Haplotypic analysis

  Abstract

Objective: Cohort and case-control genetic association studies offer the greatest power to detect small genotypic influences on disease phenotypes, relative to family-based designs. However, genetic subdivisions could confound studies involving unrelated individuals, but the topic has been little investigated. We examined geographical and interallelic association of SNP and microsatellite haplotypes of the Y chromosome, of regions of chromosome 11, and of autosomal SNP genotypes relevant to cardiovascular risk traits in a UK-wide epidemiological survey. Results: We show evidence (p = 0.00001) of the Danelaw history of the UK, marked by a two-fold excess of a Viking Y haplotype in central England. We also found evidence for a (different) single-centre geographical over-representation of one haplotype, both for APOC3-A4-A5 and for IGF2. The basis of this remains obscure but neither reflect genotyping error nor correlate with the phenotypic associations by centre of these markers. A panel of SNPs relevant to cardiovascular risks traits showed neither association with geographical location nor with Y haplotypes. Conclusion: Combinations of Y haplotyping, autosomal haplotyping, and genome-wide SNP typing, taken together with phenotypic2 associations, should improve epidemiological recognition and interpretation of possible confounding by genetic subdivision.

Copyright © 2004 S. Karger AG, Basel

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  Author Contacts

Dr. Santiago Rodríguez
Human Genetics Division, School of Medicine
University of Southampton, Duthie Building (MP808)
Southampton General Hospital, Tremona Road, Southampton SO16 6YD (UK)
Tel. +44 23 8079 4141, Fax +44 23 8079 4264, E-Mail santi@soton.ac.uk

  Article Information

Received: November 3, 2003
Accepted after revision: April 6, 2004
Number of Print Pages : 14
Number of Figures : 2, Number of Tables : 6, Number of References : 64

  Publication Details

Human Heredity (International Journal of Human and Medical Genetics)
Founded 1950 as Acta Genetica et Statistica Medica by Gunnar Dahlberg; Continued by M. Hauge (1965–1983)

Vol. 57, No. 3, Year 2004 (Cover Date: Released August 2004)

Journal Editor: J. Ott, New York, N.Y.
ISSN: 0001–5652 (print), 1423–0062 (Online)

For additional information: http://www.karger.ch/journals/hhe

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