Examining markers in 8q24 to explain differences in evidence for association with cleft lip with/without cleft palate between Asians and Europeans

Tanda Murray, Margaret A. Taub, Ingo Ruczinski, Alan F. Scott, Jacqueline B. Hetmanski, Holger Schwender, Poorav Patel, Tian Xiao Zhang, Ronald G. Munger, Allen J. Wilcox, Xiaoqian Ye, Hong Wang, Tao Wu, Yah Huei Wu-Chou, Bing Shi, Sun Ha Jee, Samuel Chong, Vincent Yeow, Jeffrey C. Murray, Mary L. MarazitaTerri H. Beaty

Research output: Contribution to journalArticlepeer-review

Abstract

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 European ancestry than among trios of Asian ancestry. We examined marker information content and haplotype diversity across 13 recruitment sites (from Europe, United States, and Asia) separately, and conducted principal components analysis (PCA) on parents. As expected, PCA revealed large genetic distances between Europeans and Asians, and a north-south cline from Korea to Singapore in Asia, with Filipino parents forming a somewhat distinct Southeast Asian cluster. Hierarchical clustering of SNP heterozygosity revealed two major clades consistent with PCA results. All genotyped SNPs giving P < 10 -6 in the allelic transmission disequilibrium test (TDT) showed higher heterozygosity in Europeans than Asians. On average, European ancestry parents had higher haplotype diversity than Asians. Imputing additional variants across chr8q24 increased the strength of statistical evidence among Europeans and also revealed a significant signal among Asians (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 Asian ancestry was not due to any distinct genetic effect, but could simply reflect low power due to lower allele frequencies in Asians.

Original languageEnglish (US)
Pages (from-to)392-399
Number of pages8
JournalGenetic epidemiology
Volume36
Issue number4
DOIs
StatePublished - May 2012

Keywords

  • 8q24
  • Cleft lip with/without cleft palate
  • Genome-wide association
  • Imputation

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)

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