Browsing by Author "Liu, Chenxing"

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    Genome scans of facial features in East Africans and cross-population comparisons reveal novel associations
    (Public Library of Science, 2021-08-19) Liu, Chenxing; Lee, Myoung Keun; Naqvi, Sahin; Hoskens, Hanne; Liu, Dongjing; White, Julie D.; Indencleef, Karlijne; Matthews, Harold; Eller, Ryan J.; Li, Jiarui; Mohammed, Jaaved; Swigut, Tomek; Richmond, Stephen; Manyama, Mange; Hallgrímsson, Benedikt; Spritz, Richard A.; Feingold, Eleanor; Marazita, Mary L.; Wysocka, Joanna; Walsh, Susan; Shriver, Mark D.; Claes, Peter; Weinberg, Seth M.; Shaffer, John R.; Biology, School of Science
    Facial morphology is highly variable, both within and among human populations, and a sizable portion of this variation is attributable to genetics. Previous genome scans have revealed more than 100 genetic loci associated with different aspects of normal-range facial variation. Most of these loci have been detected in Europeans, with few studies focusing on other ancestral groups. Consequently, the degree to which facial traits share a common genetic basis across diverse sets of humans remains largely unknown. We therefore investigated the genetic basis of facial morphology in an East African cohort. We applied an open-ended data-driven phenotyping approach to a sample of 2,595 3D facial images collected on Tanzanian children. This approach segments the face into hierarchically arranged, multivariate features that capture the shape variation after adjusting for age, sex, height, weight, facial size and population stratification. Genome scans of these multivariate shape phenotypes revealed significant (p < 2.5 × 10-8) signals at 20 loci, which were enriched for active chromatin elements in human cranial neural crest cells and embryonic craniofacial tissue, consistent with an early developmental origin of the facial variation. Two of these associations were in highly conserved regions showing craniofacial-specific enhancer activity during embryological development (5q31.1 and 12q21.31). Six of the 20 loci surpassed a stricter threshold accounting for multiple phenotypes with study-wide significance (p < 6.25 × 10-10). Cross-population comparisons indicated 10 association signals were shared with Europeans (seven sharing the same associated SNP), and facilitated fine-mapping of causal variants at previously reported loci. Taken together, these results may point to both shared and population-specific components to the genetic architecture of facial variation.
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    The Intersection of the Genetic Architectures of Orofacial Clefts and Normal Facial Variation
    (Frontiers Media, 2021-02-22) Indencleef, Karlijne; Hoskens, Hanne; Lee, Myoung Keun; White, Julie D.; Liu, Chenxing; Eller, Ryan J.; Naqvi, Sahin; Wehby, George L.; Moreno Uribe, Lina M.; Hecht, Jacqueline T.; Long, Ross E., Jr.; Christensen, Kaare; Deleyiannis, Frederic W.; Walsh, Susan; Shriver, Mark D.; Richmond, Stephen; Wysocka, Joanna; Peeters, Hilde; Shaffer, John R.; Marazita, Mary L.; Hens, Greet; Weinberg, Seth M.; Claes, Peter; Biology, School of Science
    Unaffected relatives of individuals with non-syndromic cleft lip with or without cleft palate (NSCL/P) show distinctive facial features. The presence of this facial endophenotype is potentially an expression of underlying genetic susceptibility to NSCL/P in the larger unselected population. To explore this hypothesis, we first partitioned the face into 63 partially overlapping regions representing global-to-local facial morphology and then defined endophenotypic traits by contrasting the 3D facial images from 264 unaffected parents of individuals with NSCL/P versus 3,171 controls. We observed distinct facial features between parents and controls across 59 global-to-local facial segments at nominal significance (p ≤ 0.05) and 52 segments at Bonferroni corrected significance (p < 1.2 × 10–3), respectively. Next, we quantified these distinct facial features as univariate traits in another dataset of 8,246 unaffected European individuals and performed a genome-wide association study. We identified 29 independent genetic loci that were associated (p < 5 × 10–8) with at least one of the tested endophenotypic traits, and nine genetic loci also passed the study-wide threshold (p < 8.47 × 10–10). Of the 29 loci, 22 were in proximity of loci previously associated with normal facial variation, 18 were near genes that show strong evidence in orofacial clefting (OFC), and another 10 showed some evidence in OFC. Additionally, polygenic risk scores for NSCL/P showed associations with the endophenotypic traits. This study thus supports the hypothesis of a shared genetic architecture of normal facial development and OFC.