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 Marazita; Terri H Beaty

doi:10.1002/gepi.21633

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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

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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

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, …

Genetic epidemiology, Vol.36(4), pp.392-399

05/2012

DOI: 10.1002/gepi.21633

PMCID: PMC3615645

PMID: 22508319

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Abstract

In a recent genome wide association study (GWAS) from an international consortium, evidence of linkage and association in chr8q24 was much stronger among non-syndromic 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, USA 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 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.

8q24

without cleft palate

imputation

cleft lip with

genome wide association

Details

Title: Subtitle: Examining markers in 8q24 to explain differences in evidence for association with cleft lip with/without cleft palate between Asians and Europeans
Creators: Tanda Murray - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA 21205
Margaret A Taub - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA 21205
Ingo Ruczinski - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA 21205
Alan F Scott - Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore MD, USA 21205
Jacqueline B Hetmanski - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA 21205
Holger Schwender - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA 21205
Poorav Patel - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA 21205
Tian Xiao Zhang - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA 21205
Ronald G Munger - Utah State University, Logan, UT USA 84322
Allen J Wilcox - NIEHS/NIH, Epidemiology Branch, Durham, North Carolina USA 27709
Xiaoqian Ye - Wuhan University, School of Stomatology, Wuhan, China
Hong Wang - Peking University Health Science Center, Beijing, China
Tao Wu - Peking University Health Science Center, Beijing, China
Yah Huei Wu-Chou - Chang Gung Memorial Hospital, Taoyuan, Taiwan
Bing Shi - State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu 610041, P.R. China, Chengdu, China
Sun Ha Jee - Yonsei University, Epidemiology & Health Promotion, Seoul, Korea
Samuel Chong - National University of Singapore, Singapore
Vincent Yeow - KK Women’s & Children’s Hospital, Singapore
Jeffrey C Murray - Department of Pediatrics, Children’s Hospital, University of Iowa, Iowa City, IA USA 52242
Mary L Marazita - Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA USA 15219
Terri H Beaty - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA 21205
Resource Type: Journal article
Publication Details: Genetic epidemiology, Vol.36(4), pp.392-399
DOI: 10.1002/gepi.21633
PMID: 22508319
PMCID: PMC3615645
NLM abbreviation: Genet Epidemiol
ISSN: 0741-0395
eISSN: 1098-2272
Grant note: R21 DE013707 || DE / National Institute of Dental and Craniofacial Research : NIDCR U01 DE020073 || DE / National Institute of Dental and Craniofacial Research : NIDCR U01 DE018993 || DE / National Institute of Dental and Craniofacial Research : NIDCR R01 DE014581 || DE / National Institute of Dental and Craniofacial Research : NIDCR
Language: English
Date published: 05/2012
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Internal Medicine
Record Identifier: 9984025360302771

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