A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation

Betty Bonfante (1) , Pierre Faux (1) , Nicolas Navarro (2, 3) , Javier Mendoza-Revilla (4, 5) , Morgane Dubied (2) , Charlotte Montillot (6) , Emma Wentworth (7) , Lauriane Poloni (2, 3) , Ceferino Varón-González (8) , Philip Jones (9) , Ziyi Xiong (10) , Macarena Fuentes-Guajardo (11) , Sagnik Palmal (1) , Juan Camilo Chacón-Duque (12) , Malena Hurtado (4) , Valeria Villegas (4) , Vanessa Granja (4) , Claudia Jaramillo (13) , William Arias (13) , Rodrigo Barquera (14, 15) , Paola Everardo-Martínez (14) , Mirsha Sánchez-Quinto (16) , Jorge Gómez-Valdés (14) , Hugo Villamil-Ramírez (17) , Caio Silva de Cerqueira (18) , Tábita Hünemeier (19) , Virginia Ramallo (20, 21) , Fan Liu (22, 23, 10) , Seth Weinberg (24) , John Shaffer (24) , Evie Stergiakouli (25) , Laurence Howe (25) , Pirro Hysi (26) , Timothy Spector (26) , Rolando Gonzalez-José (21) , Lavinia Schüler-Faccini (20) , Maria-Cátira Bortolini (20) , Victor Acuña-Alonzo (14) , Samuel Canizales-Quinteros (17) , Carla Gallo (4) , Giovanni Poletti (4) , Gabriel Bedoya (13) , Francisco Rothhammer (11) , Christel Thauvin-Robinet (6, 27) , Laurence Faivre (27, 6) , Caroline Costedoat (1) , David Balding (9, 28) , Timothy Cox (29) , Manfred Kayser (10) , Laurence Duplomb (6) , Binnaz Yalcin (6) , Justin Cotney (7) , Kaustubh Adhikari (9, 30) , Andrés Ruiz-Linares (1, 9, 31)

1 ADES - Anthropologie bio-culturelle, Droit, Ethique et Santé
2 BGS - Biogéosciences [UMR 6282]
3 EPHE - École Pratique des Hautes Études
4 UPCH - Universidad Peruana Cayetano Heredia
5 Génétique Evolutive Humaine - Human Evolutionary Genetics
6 Equipe GAD (LNC - U1231)
7 University of Connecticut Health Center [Farmington]
8 ISYEB - Institut de Systématique, Evolution, Biodiversité
9 UCL - University College of London [London]
10 Erasmus MC - Erasmus University Medical Center [Rotterdam]
11 Universidad de Tarapaca
12 NHM - The Natural History Museum [London]
13 Universidad de Antioquia = University of Antioquia [Medellín, Colombia]
14 NSAH - National School of Anthropology and History [Mexico City, Mexico]
15 MPI-SHH - Max Planck Institute for the Science of Human History
16 UNAM - Universidad Nacional Autónoma de México = National Autonomous University of Mexico
17 Instituto Nacional de Medicina Genomica
18 Scientific Police of São Paulo State [Ourinhos, Brazil]
19 USP - Universidade de São Paulo = University of São Paulo
20 UFRGS - Universidade Federal do Rio Grande do Sul [Porto Alegre]
21 CENPAT - Centro Nacional Patagónico
22 BGI - Beijing Genomics Institute [Shenzhen]
23 UCAS - University of Chinese Academy of Sciences [Beijing]
24 PITT - University of Pittsburgh
25 University of Bristol [Bristol]
26 King‘s College London
27 FHU TRANSLAD (CHU de Dijon)
28 University of Melbourne
29 UMKC - University of Missouri [Kansas City]
30 OU - The Open University [Milton Keynes]
31 Fudan University [Shanghai]

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.

Domaines: Sciences du Vivant [q-bio]; Anthropologie biologique

Betty Bonfante, Pierre Faux, Nicolas Navarro, Javier Mendoza-Revilla, Morgane Dubied, et al.. A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation. Science Advances , 2021, 7 (6), pp.eabc6160. ⟨10.1126/sciadv.abc6160⟩. ⟨hal-03268308⟩