A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation
Betty Bonfante, Pierre Faux, Nicolas Navarro, Javier Mendoza‐Revilla, Morgane Dubied, Charlotte Montillot, Emma Wentworth Winchester, Lauriane Poloni, Ceferino Varón‐González, Philip G. Jones, Ziyi Xiong, Macarena Fuentes‐Guajardo, Sagnik Palmal, Juan Camilo Chacón-Duque, Malena Hurtado, Valeria Villegas, Vanessa Granja, Claudia Jaramillo, William Arias, Rodrigo Barquera, Paola Everardo, Mirsha Sánchez-Quinto, Jorge Gómez‐Valdés, Hugo Villamil‐Ramírez, Caio César Silva de Cerqueira, Tábita Hünemeier, Virgínia Ramallo, Fan Liu, Seth M. Weinberg, John R. Shaffer, Evie Stergiakouli, Laurence J Howe, Pirro G. Hysi, Timothy D. Spector, Rolando González‐José, Lavínia Schüler‐Faccini, María Cátira Bortolini, Víctor Acuña-Alonzo, Samuel Canizales‐Quinteros, Carla Gallo, Giovanni Poletti, Gabriel Bedoya, Francisco Rothhammer, Christel Thauvin‐Robinet, Laurence Faivre, Caroline Costedoat, David J. Balding, Timothy C. Cox, Manfred Kayser, Laurence Duplomb, Binnaz Yalcin, Justin Cotney, Kaustubh Adhikari, Andrés Ruiz‐Linares
Abstract
To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.