PRICKLE1 × FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits
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 a...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2021-08-01
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Series: | Frontiers in Genetics |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.674642/full |
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doaj-91238ad9ea7643c09d28a76bfc1b1c3f |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dongjing Liu Hyo-Jeong Ban Ahmed M. El Sergani Ahmed M. El Sergani Myoung Keun Lee Jacqueline T. Hecht George L. Wehby Lina M. Moreno Eleanor Feingold Eleanor Feingold Mary L. Marazita Mary L. Marazita Mary L. Marazita Mary L. Marazita Seongwon Cha Heather L. Szabo-Rogers Heather L. Szabo-Rogers Heather L. Szabo-Rogers Heather L. Szabo-Rogers Seth M. Weinberg Seth M. Weinberg Seth M. Weinberg John R. Shaffer John R. Shaffer John R. Shaffer |
spellingShingle |
Dongjing Liu Hyo-Jeong Ban Ahmed M. El Sergani Ahmed M. El Sergani Myoung Keun Lee Jacqueline T. Hecht George L. Wehby Lina M. Moreno Eleanor Feingold Eleanor Feingold Mary L. Marazita Mary L. Marazita Mary L. Marazita Mary L. Marazita Seongwon Cha Heather L. Szabo-Rogers Heather L. Szabo-Rogers Heather L. Szabo-Rogers Heather L. Szabo-Rogers Seth M. Weinberg Seth M. Weinberg Seth M. Weinberg John R. Shaffer John R. Shaffer John R. Shaffer PRICKLE1 × FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits Frontiers in Genetics human facial traits variance quantitative trait loci (vQTL) gene-by-gene (G × G) interaction Prickle1 Focadhesin craniofacial |
author_facet |
Dongjing Liu Hyo-Jeong Ban Ahmed M. El Sergani Ahmed M. El Sergani Myoung Keun Lee Jacqueline T. Hecht George L. Wehby Lina M. Moreno Eleanor Feingold Eleanor Feingold Mary L. Marazita Mary L. Marazita Mary L. Marazita Mary L. Marazita Seongwon Cha Heather L. Szabo-Rogers Heather L. Szabo-Rogers Heather L. Szabo-Rogers Heather L. Szabo-Rogers Seth M. Weinberg Seth M. Weinberg Seth M. Weinberg John R. Shaffer John R. Shaffer John R. Shaffer |
author_sort |
Dongjing Liu |
title |
PRICKLE1 × FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits |
title_short |
PRICKLE1 × FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits |
title_full |
PRICKLE1 × FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits |
title_fullStr |
PRICKLE1 × FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits |
title_full_unstemmed |
PRICKLE1 × FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits |
title_sort |
prickle1 × focad interaction revealed by genome-wide vqtl analysis of human facial traits |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2021-08-01 |
description |
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 × G) interactions, which uncovered an interaction between PRICKLE1 and FOCAD affecting cranial base width. We replicated this G × G interaction signal at the locus level in an additional 5,128 Korean individuals. We used the hypomorphic Prickle1Beetlejuice (Prickle1Bj) mouse line to directly test the function of Prickle1 on the cranial base and observed wider cranial bases in Prickle1Bj/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 Prickle1Bj/Bj mutants. Taken together, our findings uncovered a novel G × 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. |
topic |
human facial traits variance quantitative trait loci (vQTL) gene-by-gene (G × G) interaction Prickle1 Focadhesin craniofacial |
url |
https://www.frontiersin.org/articles/10.3389/fgene.2021.674642/full |
work_keys_str_mv |
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doaj-91238ad9ea7643c09d28a76bfc1b1c3f2021-08-09T08:21:41ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-08-011210.3389/fgene.2021.674642674642PRICKLE1 × FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial TraitsDongjing Liu0Hyo-Jeong Ban1Ahmed M. El Sergani2Ahmed M. El Sergani3Myoung Keun Lee4Jacqueline T. Hecht5George L. Wehby6Lina M. Moreno7Eleanor Feingold8Eleanor Feingold9Mary L. Marazita10Mary L. Marazita11Mary L. Marazita12Mary L. Marazita13Seongwon Cha14Heather L. Szabo-Rogers15Heather L. Szabo-Rogers16Heather L. Szabo-Rogers17Heather L. Szabo-Rogers18Seth M. Weinberg19Seth M. Weinberg20Seth M. Weinberg21John R. Shaffer22John R. Shaffer23John R. Shaffer24Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesFuture Medicine Division, Korea Institute of Oriental Medicine, Daejeon, South KoreaCenter for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Pediatrics, McGovern Medical Center, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDepartment of Health Management and Policy, The University of Iowa, Iowa City, IA, United StatesDepartment of Orthodontics, The University of Iowa, Iowa City, IA, United StatesDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States0Department of Psychiatry, Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesFuture Medicine Division, Korea Institute of Oriental Medicine, Daejeon, South KoreaDepartment of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States1Department of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States2Regenerative Medicine at the McGowan Institute, University of Pittsburgh, Pittsburgh, PA, United States3Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United StatesThe 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 × G) interactions, which uncovered an interaction between PRICKLE1 and FOCAD affecting cranial base width. We replicated this G × G interaction signal at the locus level in an additional 5,128 Korean individuals. We used the hypomorphic Prickle1Beetlejuice (Prickle1Bj) mouse line to directly test the function of Prickle1 on the cranial base and observed wider cranial bases in Prickle1Bj/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 Prickle1Bj/Bj mutants. Taken together, our findings uncovered a novel G × 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.https://www.frontiersin.org/articles/10.3389/fgene.2021.674642/fullhuman facial traitsvariance quantitative trait loci (vQTL)gene-by-gene (G × G) interactionPrickle1Focadhesincraniofacial |