Format

Send to

Choose Destination
Hum Mol Genet. 2018 Feb 1;27(3):559-575. doi: 10.1093/hmg/ddx416.

Meta-analysis of genome-wide association studies identifies 8 novel loci involved in shape variation of human head hair.

Author information

1
Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
2
Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
3
University of Chinese Academy of Sciences, Beijing, China.
4
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
5
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
6
Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
7
Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK.
8
Department of Biology, Indiana-University-Purdue-University-Indianapolis (IUPUI), Indianapolis, IN, USA.
9
Institute of Zoology and Biomedical Research, Faculty of Biology and Earth Sciences, Jagiellonian University, Kraków, Poland.
10
Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland.
11
Department of Dermatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
12
Laboratorio de Genética Molecular, Escuela Nacional de Antropologia e Historia, México City, México.
13
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina Genómica, México City, México.
14
GENMOL (Genética Molecular), Universidad de Antioquia, Medellín, Colombia.
15
Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú.
16
Instituto de Alta Investigación, Universidad de Tarapacá, Arica, Chile.
17
Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
18
Instituto Patagónico de Ciencias Sociales y Humanas, CENPAT-CONICET, Puerto Madryn, Argentina.
19
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, Shanghai, China.
20
School of Life Science and Technology, Shanghai Tech University, Shanghai, China.
21
Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
22
Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
23
Central Forensic Laboratory of the Police, Warsaw, Poland.
24
Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai, China.
25
Laboratory of Biocultural Anthropology, Law, Ethics, and Health (Centre National de la Recherche Scientifique and Etablissement Français du Sang), Aix-Marseille Université, Marseille, France.

Abstract

Shape variation of human head hair shows striking variation within and between human populations, while its genetic basis is far from being understood. We performed a series of genome-wide association studies (GWASs) and replication studies in a total of 28 964 subjects from 9 cohorts from multiple geographic origins. A meta-analysis of three European GWASs identified 8 novel loci (1p36.23 ERRFI1/SLC45A1, 1p36.22 PEX14, 1p36.13 PADI3, 2p13.3 TGFA, 11p14.1 LGR4, 12q13.13 HOXC13, 17q21.2 KRTAP, and 20q13.33 PTK6), and confirmed 4 previously known ones (1q21.3 TCHH/TCHHL1/LCE3E, 2q35 WNT10A, 4q21.21 FRAS1, and 10p14 LINC00708/GATA3), all showing genome-wide significant association with hair shape (P < 5e-8). All except one (1p36.22 PEX14) were replicated with nominal significance in at least one of the 6 additional cohorts of European, Native American and East Asian origins. Three additional previously known genes (EDAR, OFCC1, and PRSS53) were confirmed at the nominal significance level. A multivariable regression model revealed that 14 SNPs from different genes significantly and independently contribute to hair shape variation, reaching a cross-validated AUC value of 0.66 (95% CI: 0.62-0.70) and an AUC value of 0.64 in an independent validation cohort, providing an improved accuracy compared with a previous model. Prediction outcomes of 2504 individuals from a multiethnic sample were largely consistent with general knowledge on the global distribution of hair shape variation. Our study thus delivers target genes and DNA variants for future functional studies to further evaluate the molecular basis of hair shape in humans.

PMID:
29220522
PMCID:
PMC5886212
DOI:
10.1093/hmg/ddx416
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center