Journal article
PRICKLE1 x FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits
Frontiers in genetics, Vol.12, 674642
08/09/2021
DOI: 10.3389/fgene.2021.674642
PMCID: PMC8381734
PMID: 34434215
Abstract
The human face is a highly complex and variable structure resulting from the intricate coordination of numerous genetic and non-genetic factors. Hundreds of genomic loci impacting quantitative facial features have been identified. While these associations have been shown to influence morphology by altering the mean size and shape of facial measures, their effect on trait variance remains unclear. We conducted a genome-wide association analysis for the variance of 20 quantitative facial measurements in 2,447 European individuals and identified several suggestive variance quantitative trait loci (vQTLs). These vQTLs guided us to conduct an efficient search for gene-by-gene (G x G) interactions, which uncovered an interaction between PRICKLE1 and FOCAD affecting cranial base width. We replicated this G x G interaction signal at the locus level in an additional 5,128 Korean individuals. We used the hypomorphic Prickle1(Beetlejuice) (Prickle1(Bj)) mouse line to directly test the function of Prickle1 on the cranial base and observed wider cranial bases in Prickle1(Bj/Bj). Importantly, we observed that the Prickle1 and Focadhesin proteins co-localize in murine cranial base chondrocytes, and this co-localization is abnormal in the Prickle1(Bj/Bj) mutants. Taken together, our findings uncovered a novel G x G interaction effect in humans with strong support from both epidemiological and molecular studies. These results highlight the potential of studying measures of phenotypic variability in gene mapping studies of facial morphology.
Details
- Title: Subtitle
- PRICKLE1 x FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits
- Creators
- Dongjing Liu - Icahn School of Medicine at Mount SinaiHyo-Jeong Ban - Korea Institute of Oriental MedicineAhmed M. El Sergani - University of PittsburghMyoung Keun Lee - University of PittsburghJacqueline T. Hecht - The University of Texas Health Science CenterGeorge L. Wehby - University of IowaLina M. Moreno - University of IowaEleanor Feingold - University of PittsburghMary L. Marazita - University of PittsburghSeongwon Cha - Korea Institute of Oriental MedicineHeather L. Szabo-Rogers - University of PittsburghSeth M. Weinberg - University of PittsburghJohn R. Shaffer - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- Frontiers in genetics, Vol.12, 674642
- DOI
- 10.3389/fgene.2021.674642
- PMID
- 34434215
- PMCID
- PMC8381734
- NLM abbreviation
- Front Genet
- eISSN
- 1664-8021
- Publisher
- Frontiers Media Sa
- Number of pages
- 14
- Grant note
- NRF-2018M3E3A1057298 / National Research Foundation of Korea U01-DE020078; R01-DE016148; R01-DE027023; X01-HG007821 / National Institute for Dental and Craniofacial Research (NIDCR); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) University of Pittsburgh School of Dental Medicine; University of Pittsburgh HHSN268201200008I / NIDCR; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) P30-NIH-DE020740 / Momentum Funds from the University of Pittsburgh
- Language
- English
- Date published
- 08/09/2021
- Academic Unit
- Preventive and Community Dentistry; Orthodontics; Health Management and Policy; Economics; Craniofacial Anomalies Research Center; Public Policy Center (Archive)
- Record Identifier
- 9984367642402771
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