Dataset Information

Genome-wide association study of facial morphology reveals novel associations with FREM1 and PARK2.

ABSTRACT: Several studies have now shown evidence of association between common genetic variants and quantitative facial traits in humans. The reported associations generally involve simple univariate measures and likely represent only a small fraction of the genetic loci influencing facial morphology. In this study, we applied factor analysis to a set of 276 facial linear distances derived from 3D facial surface images of 2187 unrelated individuals of European ancestry. We retained 23 facial factors, which we then tested for genetic associations using a genome-wide panel of 10,677,593 single nucleotide polymorphisms (SNPs). In total, we identified genome-wide significant (p < 5 × 10-8) associations in three regions, including two that are novel: one involving measures of midface height at 6q26 within an intron of PARK2 (lead SNP rs9456748; p = 4.99 × 10-8) and another involving measures of central upper lip height at 9p22 within FREM1 (lead SNP rs72713618; p = 2.02 × 10-8). In both cases, the genetic association was stronger with the composite facial factor phenotype than with any of the individual linear distances that comprise those factors. While the biological role of PARK2 in the craniofacial complex is currently unclear, there is evidence from both mouse models and Mendelian syndromes that FREM1 may influence facial variation. These results highlight the potential value of data-driven multivariate phenotyping for genetic studies of human facial morphology.

SUBMITTER: Lee MK

PROVIDER: S-EPMC5404842 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide association study of facial morphology reveals novel associations with FREM1 and PARK2.

Lee Myoung Keun MK Shaffer John R JR Leslie Elizabeth J EJ Orlova Ekaterina E Carlson Jenna C JC Feingold Eleanor E Marazita Mary L ML Weinberg Seth M SM

PloS one 20170425 4

Several studies have now shown evidence of association between common genetic variants and quantitative facial traits in humans. The reported associations generally involve simple univariate measures and likely represent only a small fraction of the genetic loci influencing facial morphology. In this study, we applied factor analysis to a set of 276 facial linear distances derived from 3D facial surface images of 2187 unrelated individuals of European ancestry. We retained 23 facial factors, whi ...[more]

PMID: 28441456

Similar Datasets

Project description:Genome-wide association studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks.Using pathways (gene sets) from Reactome, we carried out a 2-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CAD genome-wide association study data sets (9889 cases/11?089 controls), nominally significant gene sets were tested for replication in a meta-analysis of 9 additional studies (15?502 cases/55?730 controls) from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication P<0.05). These pathways resided in 9 of 21 core biological processes represented in Reactome, and included pathways relevant to extracellular matrix (ECM) integrity, innate immunity, axon guidance, and signaling by PDRF (platelet-derived growth factor), NOTCH, and the transforming growth factor-?/SMAD receptor complex. Many of these pathways had strengths of association comparable to those observed in lipid transport pathways. Network analysis of unique genes within the replicated pathways further revealed several interconnected functional and topologically interacting modules representing novel associations (eg, semaphoring-regulated axonal guidance pathway) besides confirming known processes (lipid metabolism). The connectivity in the observed networks was statistically significant compared with random networks (P<0.001). Network centrality analysis (degree and betweenness) further identified genes (eg, NCAM1, FYN, FURIN, etc) likely to play critical roles in the maintenance and functioning of several of the replicated pathways.These findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD.

Dataset Information

Genome-wide association study of facial morphology reveals novel associations with FREM1 and PARK2.

Publications

Genome-wide association study of facial morphology reveals novel associations with FREM1 and PARK2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets