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Genetic risk factors for orofacial clefts in Central Africans and Southeast Asians
Author(s) -
Figueiredo Jane C.,
Ly Stephanie,
Raimondi Haley,
Magee Kathy,
Baurley James W.,
SanchezLara Pedro A.,
Ihenacho Ugonna,
Yao Caroline,
Edlund Christopher K.,
van den Berg David,
Casey Graham,
DeClerk Yves A.,
Samet Jonathan M.,
Magee William
Publication year - 2014
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36693
Subject(s) - single nucleotide polymorphism , linkage disequilibrium , genome wide association study , snp , genetics , genetic association , logistic regression , biology , vietnamese , medicine , genotype , gene , linguistics , philosophy
Genome‐wide association studies (GWAS) for orofacial clefts have identified several susceptibility regions, but have largely focused on non‐Hispanic White populations in developed countries. We performed a targeted genome‐wide study of single nucleotide polymorphisms (SNPs) in exons using the Illumina HumanExome+ array with custom fine mapping of 16 cleft susceptibility regions in three underserved populations: Congolese (87 case‐mother, 210 control‐mother pairs), Vietnamese (131 case‐parent trios), and Filipinos (42 case‐mother, 99 control‐mother pairs). All cases were children with cleft lip with or without cleft palate. Families were recruited from local hospitals and parental exposures were collected using interviewer‐administered questionnaires. We used logistic regression models for case‐control analyses, family‐based association tests for trios, and fixed‐effect meta‐analyses to determine individual SNP effects corrected for multiple testing. Of the 16 known susceptibility regions tested, SNPs in four regions reached statistical significance in one or more of these populations: 1q32.2 ( IRF6 ), 10q25.3 ( VAX1 ), and 17q22 ( NOG ). Due to different linkage disequilibrium patterns, significant SNPs in these regions differed between the Vietnamese and Filipino populations from the index SNP selected from previous GWAS studies. Among Africans, there were no significant associations identified for any of the susceptibility regions. rs10787738 near VAX1 ( P = 4.98E−3) and rs7987165 ( P = 6.1E−6) were significant in the meta‐analysis of all three populations combined. These results confirm several known susceptibility regions and identify novel risk alleles in understudied populations. © 2014 Wiley Periodicals, Inc.