Evidence of admixture from haplotyping in an epidemiological study of UK Caucasian males: implications for association analyses.
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.


CONCLUSIONS
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.
Human Genetics Division, School of Medicine, University of Southampton, Southampton General Hospital, England.
Xiao-he
XH
Chen
Santiago
S
Rodríguez
Emma
E
Hawe
Philippa J
PJ
Talmud
George J
GJ
Miller
Peter
P
Underhill
Stephen E
SE
Humphries
Ian N M
IN
Day
D000483:Alleles; D001483:Base Sequence; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D041322:Chromosomes, Human, Y; D015331:Cohort Studies; D005820:Genetic Testing / Q000379:methods*; D005828:Genetics, Population; D005838:Genotype; D005843:Geography; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012107:Research Design; D017422:Sequence Analysis, DNA; D006113:United Kingdom / Q000453:epidemiology; D044465:White People