Skip to main content
Premium Trial:

Request an Annual Quote

New Facial Feature Loci Found Through GWAS Meta-Analysis

NEW YORK (GenomeWeb) – A study published online today in PLOS Genetics described new loci linked to facial features in individuals of European ancestry.

Researchers from the University of Pittsburgh and elsewhere did a meta-analysis of genome-wide association data from more than 3,100 health individuals, searching for genetic factors related to 20 facial measurements — from the distance between a person's eyes to the length and width of his or her nose.

The team's search led to more than half a dozen loci with significant ties to normal facial features. Among them were genes with known roles in face and/or skull development, as well as with genes known to be altered in individuals with facial feature-affecting syndromes.

"[M]any of these associations involve chromosomal regions harboring genes with known craniofacial function," senior author Seth Weinberg, a craniofacial and dental genetics researcher at the University of Pittsburgh, said in a statement. "Such findings can provide insights into the role genes play in the formation of the face and improve our understanding of the causal factors leading to certain craniofacial birth defects."

Several past studies have sought genetic contributors to face shape. In a 2012 study in PLOS Genetics, for example, members of the International Visible Trait Genetics Consortium described five loci linked to European facial features. And in the American Journal of Human Genetics, a UK team tapped data from the Avon Longitudinal Study of Parents and their Children to identify a PAX3 gene variant associated with nose traits in adolescents.

For a Nature Communications study published earlier this year, meanwhile, researchers from the University College London and elsewhere narrowed in on four loci associated with nose-related traits in a study of around 6,000 Latin Americans.

For the current analysis, Weinberg and his colleagues focused on 3,118 healthy individuals of European ancestry from two American cohorts who had been genotyped with Illumina arrays. They also established quantitative measurements for 20 facial landmarks with information gleaned from three-dimensional imaging.

By comparing patterns at nearly a million directly genotyped or imputed SNPs, the team uncovered loci on chromosomes 14 and 20 that were significantly associated with cranial base width. Two more loci, on the X chromosome and chromosome 1, showed significant ties to a measurement known as intercanthal width, which describes the distance between an individual's eyes. Likewise, the researchers identified a chromosome 11 site that coincided with upper facial depth. Nose width and length corresponded to variants at loci on chromosomes 20 and 14, respectively.

And when the team scrutinized some of the variants identified in past face studies in Europeans, it saw nominal ties for a variant in CACNA2D3 that was implicated in nose-related features previously. Another nose-related variant in PRDM16 was strongly associated with similar features in the cohort considered for the meta-analysis.

At least some facial measurement-associated loci found in the new study fell in or around genes such as PAX1, PAX9, and HDAC8 that have been implicated in craniofacial development or syndromes with face-related features, the authors noted, supporting the notion that similar genes contribute to normal facial morphology.

"Our ability to connect specific genetic variants to ubiquitous facial traits can inform our understanding of normal and abnormal craniofacial development, provide potential predictive models of evolutionary changes in human facial features, and improve our ability to create forensic facial reconstructions from DNA," they wrote.

In the same issue of PLOS Genetics, a team from the US, Tanzania, Canada, and the Czech Republic took a look at common variants influencing facial shape in children between the ages of three and 21 years old from the Bantu African population in Tanzania's Mwanza region.

For that GWAS, the investigators considered array-based genotyping profiles for more than 3,500 children who had had their facial features measured by three-dimensional imaging. Their analysis uncovered facial size-linked variants in the SCHIP1 and PDE8A genes — associations verified in thousands more children from the same population.

Members of the team have already followed up on the most significant associations with expression studies in mice, though they noted that future analyses may be warranted for variants at 10 loci showing more tenuous ties to face size and shape in the Bantu children.