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Using ancestry-informative markers to identify fine structure across 15 populations of European origin.

Huckins LM, Boraska V, Franklin CS, Floyd JA, Southam L, GCAN, WTCCC3, Sullivan PF, Bulik CM, Collier DA, Tyler-Smith C, Zeggini E, Tachmazidou I, GCAN, WTCCC3
Eur J Hum Genet. 2014 22 (10): 1190-200

PMID: 24549058 · PMCID: PMC4169539 · DOI:10.1038/ejhg.2014.1

The Wellcome Trust Case Control Consortium 3 anorexia nervosa genome-wide association scan includes 2907 cases from 15 different populations of European origin genotyped on the Illumina 670K chip. We compared methods for identifying population stratification, and suggest list of markers that may help to counter this problem. It is usual to identify population structure in such studies using only common variants with minor allele frequency (MAF) >5%; we find that this may result in highly informative SNPs being discarded, and suggest that instead all SNPs with MAF >1% may be used. We established informative axes of variation identified via principal component analysis and highlight important features of the genetic structure of diverse European-descent populations, some studied for the first time at this scale. Finally, we investigated the substructure within each of these 15 populations and identified SNPs that help capture hidden stratification. This work can provide information regarding the designing and interpretation of association results in the International Consortia.

MeSH Terms (14)

Anorexia Nervosa European Continental Ancestry Group Gene Frequency Genetic Markers Genetics, Population Genome-Wide Association Study Genotyping Techniques Humans Oligonucleotide Array Sequence Analysis Phylogeography Polymorphism, Single Nucleotide Principal Component Analysis Reproducibility of Results Sample Size

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