Genome-wide mapping of global-to-local genetic effects on human facial shape

被引：161

作者：

Claes, Peter ^{[1
,2
,3
]}

Roosenboom, Jasmien ^{[4
]}

White, Julie D. ^{[5
]}

Swigut, Tomek ^{[6
]}

Sero, Dzemila ^{[1
,2
]}

Li, Jiarui ^{[1
,2
]}

Lee, Myoung Keun ^{[4
]}

Zaidi, Arslan ^{[5
]}

Mattern, Brooke C. ^{[5
]}

Liebowitz, Corey ^{[5
]}

Pearson, Laurel ^{[5
]}

Gonzalez, Tomas ^{[5
]}

Leslie, Elizabeth J. ^{[4
]}

Carlson, Jenna C. ^{[7
]}

Orlova, Ekaterina ^{[8
]}

Suetens, Paul ^{[1
,2
]}

Vandermeulen, Dirk ^{[1
,2
]}

Feingold, Eleanor ^{[7
,8
]}

Marazita, Mary L. ^{[4
,8
]}

Shaffer, John R. ^{[8
]}

Wysocka, Joanna ^{[6
,9
]}

Shriver, Mark D. ^{[5
]}

Weinberg, Seth M. ^{[4
,10
]}

机构：

[1] Katholieke Univ Leuven, ESAT PSI, Dept Elect Engn, Leuven, Belgium

[2] UZ Leuven, MIRC, Leuven, Belgium

[3] Murdoch Childrens Res Inst, Melbourne, Vic, Australia

[4] Univ Pittsburgh, Dept Oral Biol, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA

[5] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA

[6] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA

[7] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA

[8] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA

[9] Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA

[10] Univ Pittsburgh, Dept Anthropol, Pittsburgh, PA 15260 USA

来源：

NATURE GENETICS | 2018年 / 50卷 / 03期

基金：

爱尔兰科学基金会;

关键词：

NEURAL CREST; ASSOCIATION; EVOLUTION; ENHANCERS; INTEGRATION; DATABASE; DISEASE;

D O I：

10.1038/s41588-018-0057-4

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample (n = 1,719). Four loci were completely new. For the others, additional support (n = 9) or pleiotropic effects (n = 2) were found in the literature, but the results reported here were further refined. All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits.

引用

页码：414 / +

页数：16

共 63 条

[1] A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation [J].

Adhikari, Kaustubh ;

Fuentes-Guajardo, Macarena ;

Quinto-Sanchez, Mirsha ;

Mendoza-Revilla, Javier ;

Chacon-Duque, Juan Camilo ;

Acuna-Alonzo, Victor ;

Jaramillo, Claudia ;

Arias, William ;

Barquera Lozano, Rodrigo ;

Macin Perez, Gaston ;

Gomez-Valdes, Jorge ;

Villamil-Ramirez, Hugo ;

Hunemeier, Tabita ;

Ramallo, Virginia ;

Silva de Cerqueira, Caio C. ;

Hurtado, Malena ;

Villegas, Valeria ;

Granja, Vanessa ;

Gallo, Carla ;

Poletti, Giovanni ;

Schuler-Faccini, Lavinia ;

Salzano, Francisco M. ;

Bortolini, Maria-Catira ;

Canizales-Quinteros, Samuel ;

Cheeseman, Michael ;

Rosique, Javier ;

Bedoya, Gabriel ;

Rothhammer, Francisco ;

Headon, Denis ;

Gonzalez-Jose, Rolando ;

Balding, David ;

Ruiz-Linares, Andres .

NATURE COMMUNICATIONS, 2016, 7

[2] An ENU-induced mutation in AP-2α leads to middle ear and ocular defects in Doarad mice [J].

Ahituv, N ;

Erven, A ;

Fuchs, H ;

Guy, K ;

Ashery-Padan, R ;

Williams, T ;

de Angelis, MH ;

Avraham, KB ;

Steel, KP .

MAMMALIAN GENOME, 2004, 15 (06) :424-432

[3] Fast model-based estimation of ancestry in unrelated individuals [J].

Alexander, David H. ;

Novembre, John ;

Lange, Kenneth .

GENOME RESEARCH, 2009, 19 (09) :1655-1664

[4] An integrated map of genetic variation from 1,092 human genomes [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Schmidt, Jeanette P. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Dinh, Huyen ;

Kovar, Christie ;

Lee, Sandra ;

Lewis, Lora ;

Muzny, Donna ;

Reid, Jeff ;

Wang, Min ;

Wang, Jun ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Li, Zhuo ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Su, Zhe ;

Tai, Shuaishuai ;

Tang, Meifang .

NATURE, 2012, 491 (7422) :56-65

[5]

Benjamini Y, 2001, ANN STAT, V29, P1165

[6] An Expanded View of Complex Traits: From Polygenic to Omnigenic [J].

Boyle, Evan A. ;

Li, Yang I. ;

Pritchard, Jonathan K. .

CELL, 2017, 169 (07) :1177-1186

[7] Development and evolution of the neural crest: An overview [J].

Bronner, Marianne E. ;

LeDouarin, Nicole M. .

DEVELOPMENTAL BIOLOGY, 2012, 366 (01) :2-9

[8]

Carlson DS, 2005, SEMINARS ORTHODONTIC, V11, P172, DOI DOI 10.1053/J.SODO.2005.07.002

[9] Improved facial outcome assessment using a 3D anthropometric mask [J].

Claes, P. ;

Walters, M. ;

Clement, J. .

INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, 2012, 41 (03) :324-330

[10] Modeling 3D Facial Shape from DNA [J].

Claes, Peter ;

Liberton, Denise K. ;

Daniels, Katleen ;

Rosana, Kerri Matthes ;

Quillen, Ellen E. ;

Pearson, Laurel N. ;

McEvoy, Brian ;

Bauchet, Marc ;

Zaidi, Arslan A. ;

Yao, Wei ;

Tang, Hua ;

Barsh, Gregory S. ;

Absher, Devin M. ;

Puts, David A. ;

Rocha, Jorge ;

Beleza, Sandra ;

Pereira, Rinaldo W. ;

Baynam, Gareth ;

Suetens, Paul ;

Vandermeulen, Dirk ;

Wagner, Jennifer K. ;

Boster, James S. ;

Shriver, Mark D. .

PLOS GENETICS, 2014, 10 (03)

← 1 2 3 4 5 6 7 →