Genetic risk factors for orofacial clefts in Central Africans and Southeast Asians1. Issue 10 (5th August 2014)

• Record Type: Journal Article
• Authors: Figueiredo, Jane C.; Ly, Stephanie; Raimondi, Haley; Magee, Kathy; Baurley, James W.; Sanchez‐Lara, Pedro A.; Ihenacho, Ugonna; Yao, Caroline; Edlund, Christopher K.; van den Berg, David; Casey, Graham; DeClerk, Yves A.; Samet, Jonathan M.; Magee, William
• Is Part Of: American journal of medical genetics. Volume 164:Issue 10(2014.)
• Page Start: 2572
• Page End: 2580
• Publication Date: 2014-08-05
• Subjects: GWAS -- VAX1 -- IRF6 -- GREM1 -- NOG -- CL(P); Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36693
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract : 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.