TY - JOUR
T1 - Meta-analysis of genome-wide association studies identifies 8 novel loci involved in shape variation of human head hair
AU - Liu, Fan
AU - Chen, Yan
AU - Zhu, Gu
AU - Hysi, Pirro G.
AU - Wu, Sijie
AU - Adhikari, Kaustubh
AU - Breslin, Krystal
AU - Pośpiech, Ewelina
AU - Hamer, Merel A.
AU - Peng, Fuduan
AU - Muralidharan, Charanya
AU - Acuna-Alonzo, Victor
AU - Canizales-Quinteros, Samuel
AU - Bedoya, Gabriel
AU - Gallo, Carla
AU - Poletti, Giovanni
AU - Rothhammer, Francisco
AU - Bortolini, Maria Catira
AU - Gonzalez-Jose, Rolando
AU - Zeng, Changqing
AU - Xu, Shuhua
AU - Jin, Li
AU - Uitterlinden, André G.
AU - Arfan Ikram, M.
AU - van Duijn, Cornelia M.
AU - Nijsten, Tamar
AU - Walsh, Susan
AU - Branicki, Wojciech
AU - Wang, Sijia
AU - Ruiz-Linares, Andrés
AU - Spector, Timothy D.
AU - Martin, Nicholas G.
AU - Medland, Sarah E.
AU - Kayser, Manfred
N1 - Publisher Copyright:
© The Author(s) 2017. Published by Oxford University Press. All rights reserved.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85042605116
U2 - 10.1093/hmg/ddx416
DO - 10.1093/hmg/ddx416
M3 - Artículo
C2 - 29220522
AN - SCOPUS:85042605116
SN - 0964-6906
VL - 27
SP - 559
EP - 575
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 3
ER -