A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13.

A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13.

Human molecular genetics (2016-04-02)

Elizabeth J Leslie, Jenna C Carlson, John R Shaffer, Eleanor Feingold, George Wehby, Cecelia A Laurie, Deepti Jain, Cathy C Laurie, Kimberly F Doheny, Toby McHenry, Judith Resick, Carla Sanchez, Jennifer Jacobs, Beth Emanuele, Alexandre R Vieira, Katherine Neiswanger, Andrew C Lidral, Luz Consuelo Valencia-Ramirez, Ana Maria Lopez-Palacio, Dora Rivera Valencia, Mauricio Arcos-Burgos, Andrew E Czeizel, L Leigh Field, Carmencita D Padilla, Eva Maria C Cutiongco-de la Paz, Frederic Deleyiannis, Kaare Christensen, Ronald G Munger, Rolv T Lie, Allen Wilcox, Paul A Romitti, Eduardo E Castilla, Juan C Mereb, Fernando A Poletta, Iêda M Orioli, Flavia M Carvalho, Jacqueline T Hecht, Susan H Blanton, Carmen J Buxó, Azeez Butali, Peter A Mossey, Wasiu L Adeyemo, Olutayo James, Ramat O Braimah, Babatunde S Aregbesola, Mekonen A Eshete, Fikre Abate, Mine Koruyucu, Figen Seymen, Lian Ma, Javier Enríquez de Salamanca, Seth M Weinberg, Lina Moreno, Jeffrey C Murray, Mary L Marazita

PMID27033726

摘要

Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental factors. Previous genome-wide association studies (GWASs) have identified at least 15 risk loci for CL/P. As these loci do not account for all of the genetic variance of CL/P, we hypothesized the existence of additional risk loci. We conducted a multiethnic GWAS in 6480 participants (823 unrelated cases, 1700 unrelated controls and 1319 case-parent trios) with European, Asian, African and Central and South American ancestry. Our GWAS revealed novel associations on 2p24 near FAM49A, a gene of unknown function (P = 4.22 × 10