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

Title
Examining markers in 8q24 to explain differences in evidence for association with cleft lip with/without cleft palate between Asians and Europeans.
Authors
Tanda Murray;Margaret A. Taub;Terri H. Beaty;Mary L. Marazita;Jeffrey C. Murray;Vincent Yeow;Samuel Chong;Sun Ha Jee;Bing Shi;Yah Huei Wu-Chou;Tao Wu;Hong Wang;Xiaoqian Ye;Allen J. Wilcox;Ronald G. Munger;Tian Xiao Zhang;Poorav Patel;Holger Schwender;Jacqueline B. Hetmanski;Alan F. Scott;Ingo Ruczinski
Issue Date
2012
Journal Title
Genetic Epidemiology
ISSN
0741-0395
Citation
Genetic Epidemiology, Vol.36(4) : 392~399, 2012
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.
URI

http://ir.ymlib.yonsei.ac.kr/handle/22282913/90310
Appears in Collections:
1. 연구논문 > 4. Graduate School of Public Health > Graduate School of Public Health
Yonsei Authors
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