A genome-wide association study identifies multiple loci for variation in human ear morphology

Abstract

Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10−8 to 3 × 10−14). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1.

The Genetic Diversity of the Americas

“…There is a strong and significant correlation between the average estimates of Native American, European, and African genetic ancestry and the frequency of the equivalent perceived ancestry categories reported in population survey data for these territories ( Figure 5): for native ancestry, R = 0.66 (p = 7  10 4 ); for European ancestry, R = 0.92 (p = 2  10 9 ); and for African ancestry, R = 0.96 (p = 4  10 12 ). The correlation between perceived and genetically estimated ancestry is consistent with the fact that physical appearance is partly genetic (1,2,4,82) and likely an important determinant of perception of ancestry. The review of genetic data underpins the interpretation of ancestry perception data in that, globally, variation in Native, European and African ancestry across the Western Hemisphere bears the imprint of the region's colonial history.…”

Latin Americans show wide-spread Converso ancestry and the imprint of local Native ancestry on physical appearance

“…A structured interview recorded the birthplace of volunteers and their ancestors (up to grandparents), as well as information on the language(s) spoken by them. We have previously reported genome-wide association studies based on Illumina OmniExpress chip data obtained in these individuals 22,24,25 .…”

“…PLINK v1.9 26,27 was used to exclude SNPs and individuals with more than 5% missing data, markers with minor allele frequency <1%, related individuals, and those who failed the Xchromosome sex concordance check. The same QC filters had been applied to the CANDELA dataset 22,24,25 . Individuals born outside the country were relocated when coming from one of the five countries included in this study or otherwise removed.…”

“…These traits have been described in detail previously 4,22,24,25 and brief definitions are provided in Supplementary text 5. To evaluate the phenotypic effect of sub-continental ancestry components defined by SOURCEFIND we used linear regression.…”

Predicting Physical Features and Diseases by DNA Analysis: Current Advances and Future Challenges

“…However, FDP technology, as well as the characterisation of PIMs, is only possible thanks to the effort and intensification of investments by funding agencies in these types of research. Initiatives such as CANDELA (Consortium for the Analysis of the Diversity and Evolution in Latin America) [20,21] and GIANT (Genetic Investigation of ANthropocentric Traits) [22,23] are examples of basic and applied research in these areas.…”