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

• Autores: Liu, Fan; Chen, Yan; Zhu, Gu; Hysi, Pirro G.; Wu, Sijie; Adhikari, Kaustubh; Breslin, Krystal; Pośpiech, Ewelina; Hamer, Merel A.; Peng, Fuduan; Muralidharan, Charanya; Acuna Alonzo, Victor; Canizales Quinteros, Samuel; Bedoya, Gabriel; Gallo, Carla; Poletti, Giovanni; Rothhammer, Francisco; Bortolini, Maria Catira; González José, Rolando; Zeng, Changqing; Xu, Shuhua; Jin, Li; Uitterlinden, André G.; Ikram, M. Arfan; van Duijn, Cornelia M.; Nijsten, Tamar; Walsh, Susan; Branicki, Wojciech; Wang, Sijia; Ruiz Linares, Andrés; Spector, Timothy D.; Martin, Nicholas G.; Medland, Sarah E.; Kayser, Manfred
• Año de publicación: 2018
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Genes; Genome; Hair; Single Nucleotide Polymorphism; Genetics; Native Americans; Asian; Genome-Wide Association Study
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Liu, Fan. Chinese Academy of Sciences; República de China. Erasmus MC University Medical Center Rotterdam; Países Bajos
Fil: Chen, Yan. Chinese Academy of Sciences; República de China
Fil: Zhu, Gu. QIMR Berghofer Medical Research Institute; Australia
Fil: Hysi, Pirro G.. King’s College London; Reino Unido
Fil: Wu, Sijie. Chinese Academy of Sciences; República de China
Fil: Adhikari, Kaustubh. Colegio Universitario de Londres; Reino Unido
Fil: Breslin, Krystal. Indiana University; Estados Unidos. Purdue University; Estados Unidos
Fil: Pośpiech, Ewelina. Jagiellonian University; Polonia
Fil: Hamer, Merel A.. Erasmus MC University Medical Center Rotterdam; Países Bajos
Fil: Peng, Fuduan. Chinese Academy of Sciences; República de China
Fil: Muralidharan, Charanya. Indiana University; Estados Unidos. Purdue University; Estados Unidos
Fil: Acuna Alonzo, Victor. Escuela Nacional de Antropologia e Historia; México
Fil: Canizales Quinteros, Samuel. Universidad Nacional Autónoma de México; México
Fil: Bedoya, Gabriel. Universidad de Antioquia; Colombia
Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú
Fil: Poletti, Giovanni. Universidad Peruana Cayetano Heredia; Perú
Fil: Rothhammer, Francisco. Universidad de Tarapacá; Chile
Fil: Bortolini, Maria Catira. Universidade Federal do Rio Grande do Sul; Brasil
Fil: González José, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina
Fil: Zeng, Changqing. Chinese Academy of Sciences; República de China
Fil: Xu, Shuhua. Chinese Academy of Sciences; República de China. Fudan University; China. Shanghai Tech University; China
Fil: Jin, Li. University of Chinese Academy of Sciences; China. Fudan University; China
Fil: Uitterlinden, André G.. Erasmus MC University Medical Center Rotterdam; Países Bajos
Fil: Ikram, M. Arfan. Erasmus MC University Medical Center Rotterdam; Países Bajos
Fil: van Duijn, Cornelia M.. Erasmus MC University Medical Center Rotterdam; Países Bajos
Fil: Nijsten, Tamar. Erasmus MC University Medical Center Rotterdam; Países Bajos
Fil: Walsh, Susan. Indiana University; Estados Unidos. Purdue University; Estados Unidos
Fil: Branicki, Wojciech. Jagiellonian University; Polonia. Central Forensic Laboratory of the Police; Polonia
Fil: Wang, Sijia. Chinese Academy of Sciences; República de China. Fudan University; China
Fil: Ruiz Linares, Andrés. Colegio Universitario de Londres; Reino Unido. Fudan University; China. Aix-Marseille Université; Francia
Fil: Spector, Timothy D.. King’s College London; Reino Unido
Fil: Martin, Nicholas G.. QIMR Berghofer Medical Research Institute; Australia
Fil: Medland, Sarah E.. QIMR Berghofer Medical Research Institute; Australia
Fil: Kayser, Manfred. Erasmus MC University Medical Center Rotterdam; Países Bajos