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Examining Markers in 8q24 to Explain Differences in Evidence for Association With Cleft Lip With/Without Cleft Palate Between A sians and E uropeans
Author(s) -
Murray Tanda,
Taub Margaret A.,
Ruczinski Ingo,
Scott Alan F.,
Hetmanski Jacqueline B.,
Schwender Holger,
Patel Poorav,
Zhang Tian Xiao,
Munger Ronald G.,
Wilcox Allen J.,
Ye Xiaoqian,
Wang Hong,
Wu Tao,
WuChou Yah Huei,
Shi Bing,
Jee Sun Ha,
Chong Samuel,
Yeow Vincent,
Murray Jeffrey C.,
Marazita Mary L.,
Beaty Terri H.
Publication year - 2012
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.21633
Subject(s) - linkage disequilibrium , genetics , biology , loss of heterozygosity , genome wide association study , snp , genetic association , allele , haplotype , transmission disequilibrium test , single nucleotide polymorphism , population , ancestry informative marker , genetic diversity , evolutionary biology , allele frequency , genotype , demography , gene , sociology
In a recent genome‐wide association study ( GWAS ) from an international consortium, evidence of linkage and association in chr8q24 was much stronger among nonsyndromic cleft lip/palate ( CL / P ) case‐parent trios of E uropean ancestry than among trios of A sian ancestry. We examined marker information content and haplotype diversity across 13 recruitment sites (from E urope, U nited S tates, and A sia) separately, and conducted principal components analysis ( PCA ) on parents. As expected, PCA revealed large genetic distances between E uropeans and A sians, and a north‐south cline from K orea to S ingapore in A sia, with F ilipino parents forming a somewhat distinct S outheast A sian cluster. Hierarchical clustering of SNP heterozygosity revealed two major clades consistent with PCA results. All genotyped SNP s giving P < 10 −6 in the allelic transmission disequilibrium test ( TDT ) showed higher heterozygosity in E uropeans than A sians. On average, E uropean ancestry parents had higher haplotype diversity than A sians. Imputing additional variants across chr8q24 increased the strength of statistical evidence among E uropeans and also revealed a significant signal among A sians (although it did not reach genome‐wide significance). Tests for SNP ‐population interaction were negative, indicating the lack of strong signal for 8q24 in families of A sian ancestry was not due to any distinct genetic effect, but could simply reflect low power due to lower allele frequencies in A sians. Genet. Epidemiol. 36:392–399, 2012. © 2012 Wiley Periodicals, Inc.