A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation

被引：133

作者：

Adhikari, Kaustubh ^{[1
]}

Fuentes-Guajardo, Macarena ^{[1
,2
]}

Quinto-Sanchez, Mirsha ^{[3
]}

Mendoza-Revilla, Javier ^{[1
,4
]}

Chacon-Duque, Juan Camilo ^{[1
]}

Acuna-Alonzo, Victor ^{[1
,5
]}

Jaramillo, Claudia ^{[6
]}

Arias, William ^{[6
]}

Barquera Lozano, Rodrigo ^{[5
,7
]}

Macin Perez, Gaston ^{[5
,7
]}

Gomez-Valdes, Jorge ^{[8
]}

Villamil-Ramirez, Hugo ^{[7
]}

Hunemeier, Tabita ^{[9
,16
]}

Ramallo, Virginia ^{[3
,9
]}

Silva de Cerqueira, Caio C. ^{[3
,9
]}

Hurtado, Malena ^{[4
]}

Villegas, Valeria ^{[4
]}

Granja, Vanessa ^{[4
]}

Gallo, Carla ^{[4
]}

Poletti, Giovanni ^{[4
]}

Schuler-Faccini, Lavinia ^{[9
]}

Salzano, Francisco M. ^{[9
]}

Bortolini, Maria-Catira ^{[9
]}

Canizales-Quinteros, Samuel ^{[7
]}

Cheeseman, Michael ^{[10
,11
]}

Rosique, Javier ^{[12
]}

Bedoya, Gabriel ^{[6
]}

Rothhammer, Francisco ^{[13
]}

Headon, Denis ^{[10
,11
]}

Gonzalez-Jose, Rolando ^{[3
]}

Balding, David ^{[1
,14
,15
]}

Ruiz-Linares, Andres ^{[1
]}

机构：

[1] UCL, Genet Inst, Dept Genet Evolut & Environm, Mortimer St, London WC1E 6BT, England

[2] Univ Tarapaca, Fac Ciencias Salud, Dept Tecnol Med, Arica 1000009, Chile

[3] Consejo Nacl Invest Cient & Tecn, Ctr Nacl Patagon, Unidad Diversidad Sistemat & Evoluc, Puerto Madryn U912OACD, RA-1033 Buenos Aires, DF, Argentina

[4] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Labs Invest & Desarrollo, Lima 31, Peru

[5] Escuela Nacl Antropol & Hist, Genet Mol Lab, Mexico City 14030, DF, Mexico

[6] Univ Antioquia, GENMOL Genet Mol, Medellin 5001000, Colombia

[7] UNAM Inst Nacl Med Genom, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City 4510, DF, Mexico

[8] Univ Nacl Autonoma Mexico, Dept Anat, Fac Med, Mexico City 04510, DF, Mexico

[9] Univ Fed Rio Grande do Sul, Dept Genet, BR-91501970 Porto Alegre, RS, Brazil

[10] Univ Edinburgh, Roslin Inst, Div Dev Biol, Roslin EH25 9RG, Midlothian, Scotland

[11] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin EH25 9RG, Midlothian, Scotland

[12] Univ Antioquia, Dept Antropol, Medellin 5001000, Colombia

[13] Univ Tarapaca, Inst Alta Invest, Arica 1000000, Chile

[14] Univ Melbourne, Sch Biosci, Melbourne, Vic 3010, Australia

[15] Univ Melbourne, Sch Math & Stat, Melbourne, Vic 3010, Australia

[16] Univ Sao Paulo, Dept Genet & Biol Evolut, BR-05508090 Sao Paulo, Brazil

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会;

关键词：

GENOTYPE IMPUTATION; POPULATION HISTORY; ANCESTRY; VARIANT; MICE; VISUALIZATION; HERITABILITY; NEANDERTHAL; MUTATIONS; REGULATOR;

D O I：

10.1038/ncomms11616

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We report a genome-wide association scan for facial features in similar to 6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values <5 x 10(-8)) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of similar to 3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion.

引用

页数：11

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