Dataset Information

A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation.

ABSTRACT: To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.

SUBMITTER: Bonfante B

PROVIDER: S-EPMC7864580 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation.

Bonfante Betty B Faux Pierre P Navarro Nicolas N Mendoza-Revilla Javier J Dubied Morgane M Montillot Charlotte C Wentworth Emma E Poloni Lauriane L Varón-González Ceferino C Jones Philip P Xiong Ziyi Z Fuentes-Guajardo Macarena M Palmal Sagnik S Chacón-Duque Juan Camilo JC Hurtado Malena M Villegas Valeria V Granja Vanessa V Jaramillo Claudia C Arias William W Barquera Rodrigo R Everardo-Martínez Paola P Sánchez-Quinto Mirsha M Gómez-Valdés Jorge J Villamil-Ramírez Hugo H Silva de Cerqueira Caio C CC Hünemeier Tábita T Ramallo Virginia V Liu Fan F Weinberg Seth M SM Shaffer John R JR Stergiakouli Evie E Howe Laurence J LJ Hysi Pirro G PG Spector Timothy D TD Gonzalez-José Rolando R Schüler-Faccini Lavinia L Bortolini Maria-Cátira MC Acuña-Alonzo Victor V Canizales-Quinteros Samuel S Gallo Carla C Poletti Giovanni G Bedoya Gabriel G Rothhammer Francisco F Thauvin-Robinet Christel C Faivre Laurence L Costedoat Caroline C Balding David D Cox Timothy T Kayser Manfred M Duplomb Laurence L Yalcin Binnaz B Cotney Justin J Adhikari Kaustubh K Ruiz-Linares Andrés A

Science advances 20210205 6

To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported unt ...[more]

PMID: 33547071

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Project description:BACKGROUND:Patients with facial nerve paralysis (FNP) experience challenges in accessing health care that could potentially be overcome by telemedicine. However, the reliability of telemedicine has yet to be established in this field. OBJECTIVE:This study aimed to investigate the consistency between face-to-face and video assessments of patients with FNP by experienced clinicians. METHODS:A repeated-measures design was used. A total of 7 clinicians assessed the FNP of 28 patients in a face-to-face clinic using standardized grading systems (the House-Brackmann, Sydney, and Sunnybrook facial grading systems). After 3 months, the same grading systems were used to assess facial palsy in video recordings of the same patients. RESULTS:The House-Brackmann system in video assessment had excellent reliability and agreement (intraclass correlation coefficient [ICC]=0.780; principal component analysis [PCA]=87.5%), similar to face-to-face assessment (ICC=0.686; PCA=79.2%). Reliability of the Sydney system was good to excellent, with excellent agreement face-to-face (ICC=0.633 to 0.834; PCA=81.0%-95.2%). However, video assessment of the cervical branch and synkinesis had fair reliability and good agreement (ICC=0.437 to 0.597; PCA=71.4%), whereas that of other branches had good to excellent reliability and excellent agreement (ICC=0.625 to 0.862; PCA=85.7%-100.0%). Reliability of the Sunnybrook system was poor to fair for resting symmetry (ICC=0.195 to 0.498; PCA=91.3%-100.0%) and synkinesis (ICC=-0.037 to 0.637; PCA=69.6%-87.0%) but was good to excellent for voluntary movement (ICC=0.601 to 0.906; PCA=56.5%-91.3%) in face-to-face and video assessments. Bland-Altman plots indicated normal limits of agreement within ±1 between face-to-face and video-assessed scores only for the temporal and buccal branches of the Sydney system and for resting symmetry in the Sunnybrook system. CONCLUSIONS:Video assessment of FNP with the House-Brackmann and Sunnybrook systems was as reliable as face-to-face but with insufficient agreement, especially in the assessment of synkinesis. However, video assessment does not account for the impact of real-time interactions that occur during tele-assessment sessions.

Project description:BackgroundDental caries is the most common chronic disease in the US and disproportionately affects racial/ethnic minorities. Caries is heritable, and though genetic heterogeneity exists between ancestries for a substantial portion of loci associated with complex disease, a genome-wide association study (GWAS) of caries specifically in African Americans has not been performed previously.MethodsWe performed exploratory GWAS of dental caries in 109 African American adults (age > 18) and 96 children (age 3-12) from the Center for Oral Health Research in Appalachia (COHRA1 cohort). Caries phenotypes (DMFS, DMFT, dft, and dfs indices) assessed by dental exams were tested for association with 5 million genotyped or imputed single nucleotide polymorphisms (SNPs), separately in the two age groups. The GWAS was performed using linear regression with adjustment for age, sex, and two principal components of ancestry. A maximum of 1 million adaptive permutations were run to determine empirical significance.ResultsNo loci met the threshold for genome-wide significance, though some of the strongest signals were near genes previously implicated in caries such as antimicrobial peptide DEFB1 (rs2515501; p = 4.54 × 10- 6) and TUFT1 (rs11805632; p = 5.15 × 10- 6). Effect estimates of lead SNPs at suggestive loci were compared between African Americans and Caucasians (adults N = 918; children N = 983). Significant (p < 5 × 10- 8) genetic heterogeneity for caries risk was found between racial groups for 50% of the suggestive loci in children, and 12-18% of the suggestive loci in adults.ConclusionsThe genetic heterogeneity results suggest that there may be differences in the contributions of genetic variants to caries across racial groups, and highlight the critical need for the inclusion of minorities in subsequent and larger genetic studies of caries in order to meet the goals of precision medicine and to reduce oral health disparities.

Dataset Information

A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation.

Publications

A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation.

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