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Hum Genet. 2016 Jan;135(1):99-108. doi: 10.1007/s00439-015-1618-6. Epub 2015 Nov 24.

EDARV370A associated facial characteristics in Uyghur population revealing further pleiotropic effects.

Peng Q1,2, Li J1,2, Tan J2, Yang Y2,3, Zhang M1,2, Wu S1,2, Liu Y1,2, Zhang J2,3, Qin P1, Guan Y4, Jiao Y4, Zhang Z4, Sabeti PC5,6, Tang K1, Xu S1,2,7, Jin L8,9,10, Wang S11,12.

Author information

1
Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, 200031, Shanghai, China.
2
State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 200433, Shanghai, China.
3
Fudan-Taizhou Institute of Health Sciences, 1 Yaocheng Road, 225300, Taizhou, Jiangsu, China.
4
Department of Biochemistry, Preclinical Medicine College, Xinjiang Medical University, 830011, Urumqi, Xinjiang, China.
5
The Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
6
Department of Organismic and Evolutionary Biology, Center for Systems Biology, Cambridge, MA, 02138, USA.
7
School of Life Science and Technology, Shanghai Tec University, 200031, Shanghai, China.
8
Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, 200031, Shanghai, China. lijin@fudan.edu.cn.
9
State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 200433, Shanghai, China. lijin@fudan.edu.cn.
10
Fudan-Taizhou Institute of Health Sciences, 1 Yaocheng Road, 225300, Taizhou, Jiangsu, China. lijin@fudan.edu.cn.
11
Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, 200031, Shanghai, China. wangsijia@picb.ac.cn.
12
State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 200433, Shanghai, China. wangsijia@picb.ac.cn.

Abstract

An adaptive variant of human Ectodysplasin receptor, EDARV370A, had undergone strong positive selection in East Asia. In mice and humans, EDARV370A was found to affect ectodermal-derived characteristics, including hair thickness, hair shape, active sweat gland density and teeth formation. Facial characteristics are also largely ectodermal derived. In this study, taking advantage of an admixed population of East Asian and European ancestry-the Uyghur, we aim to test whether EDARV370A is affecting facial characteristics and to investigate its pleiotropic nature and genetic model. In a sample of 1027 Uyghurs, we discover that EDARV370A is significantly associated with several facial characteristics, in particular shape of earlobe (P = 3.64 × 10 (-6) ) and type of chin (P = 9.23 × 10 (-5) ), with successful replication in other East Asian populations. Additionally, in this Uyghur population, we replicate previous association findings of incisors shoveling (P = 1.02 × 10 (-7) ), double incisors shoveling (P = 1.86 × 10 (-12) ) and hair straightness (P = 3.99 × 10 (-16) ), providing strong evidence supporting an additive model for the EDARV370A associations. Partial least square path model confirms EDARV370A systematically affect these weakly related ectodermal-derived characteristics, suggesting the pleiotropic effect of EDARV370A mainly plays roles in early embryo development. This study extends our knowledge about the pleiotropic nature of EDARV370A and provides potential clues to its adaptation fitness in human evolution.

KEYWORDS:

Association study; EDARV370A; Facial characteristics; Pleiotropic effect; Uyghur

PMID:
26603699
DOI:
10.1007/s00439-015-1618-6
[Indexed for MEDLINE]

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