Dataset Information

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

ABSTRACT: We report a genome-wide association scan for facial features in ?6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10(-8)) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ?3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion.

SUBMITTER: Adhikari K

PROVIDER: S-EPMC4874031 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Adhikari Kaustubh K Fuentes-Guajardo Macarena M Quinto-Sánchez Mirsha M Mendoza-Revilla Javier J Camilo Chacón-Duque Juan J Acuña-Alonzo Victor V Jaramillo Claudia C Arias William W Lozano Rodrigo Barquera RB Pérez Gastón Macín GM Gómez-Valdés Jorge J Villamil-Ramírez Hugo H Hunemeier Tábita T Ramallo Virginia V Silva de Cerqueira Caio C CC Hurtado Malena M Villegas Valeria V Granja Vanessa V Gallo Carla C Poletti Giovanni G Schuler-Faccini Lavinia L Salzano Francisco M FM Bortolini Maria-Cátira MC Canizales-Quinteros Samuel S Cheeseman Michael M Rosique Javier J Bedoya Gabriel G Rothhammer Francisco F Headon Denis D González-José Rolando R Balding David D Ruiz-Linares Andrés A

Nature communications 20160519

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10(-8)) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, ...[more]

PMID: 27193062

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Project description:Diarrhea is a major cause of both morbidity and mortality worldwide, especially among young children. Cryptosporidiosis is a leading cause of diarrhea in children, particularly in South Asia and sub-Saharan Africa, where it is responsible for over 200,000 deaths per year. Beyond the initial clinical presentation of diarrhea, it is associated with long-term sequelae such as malnutrition and neurocognitive developmental deficits. Risk factors include poverty and overcrowding, and yet not all children with these risk factors and exposure are infected, nor do all infected children develop symptomatic disease. One potential risk factor to explain these differences is their human genome. To identify genetic variants associated with symptomatic cryptosporidiosis, we conducted a genome-wide association study (GWAS) examining 6.5 million single nucleotide polymorphisms (SNPs) in 873 children from three independent cohorts in Dhaka, Bangladesh, namely, the Dhaka Birth Cohort (DBC), the Performance of Rotavirus and Oral Polio Vaccines in Developing Countries (PROVIDE) study, and the Cryptosporidiosis Birth Cohort (CBC). Associations were estimated separately for each cohort under an additive model, adjusting for length-for-age Z-score at 12?months of age, the first two principal components to account for population substructure, and genotyping batch. The strongest meta-analytic association was with rs58296998 (P?=?3.73?×?10-8), an intronic SNP and expression quantitative trait locus (eQTL) of protein kinase C alpha (PRKCA). Each additional risk allele conferred 2.4 times the odds of Cryptosporidium-associated diarrhea in the first year of life. This genetic association suggests a role for protein kinase C alpha in pediatric cryptosporidiosis and warrants further investigation.IMPORTANCE Globally, diarrhea remains one of the major causes of pediatric morbidity and mortality. The initial symptoms of diarrhea can often lead to long-term consequences for the health of young children, such as malnutrition and neurocognitive developmental deficits. Despite many children having similar exposures to infectious causes of diarrhea, not all develop symptomatic disease, indicating a possible role for human genetic variation. Here, we conducted a genetic study of susceptibility to symptomatic disease associated with Cryptosporidium infection (a leading cause of diarrhea) in three independent cohorts of infants from Dhaka, Bangladesh. We identified a genetic variant within protein kinase C alpha (PRKCA) associated with higher risk of cryptosporidiosis in the first year of life. These results indicate a role for human genetics in susceptibility to cryptosporidiosis and warrant further research to elucidate the mechanism.

Dataset Information

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

Publications

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

Similar Datasets

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