Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu Africans
Similarity in facial characteristics between relatives suggests a strong genetic component underlies facial variation. While there have been numerous studies of the genetics of facial abnormalities and, more recently, single nucleotide polymorphism (SNP) genome-wide association studies (GWASs) of no...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | HGG Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666247721000634 |
| _version_ | 1818753602473164800 |
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| author | Megan Null Feyza Yilmaz David Astling Hung-Chun Yu Joanne B. Cole Benedikt Hallgrímsson Stephanie A. Santorico Richard A. Spritz Tamim H. Shaikh Audrey E. Hendricks |
| author_facet | Megan Null Feyza Yilmaz David Astling Hung-Chun Yu Joanne B. Cole Benedikt Hallgrímsson Stephanie A. Santorico Richard A. Spritz Tamim H. Shaikh Audrey E. Hendricks |
| author_sort | Megan Null |
| collection | DOAJ |
| description | Similarity in facial characteristics between relatives suggests a strong genetic component underlies facial variation. While there have been numerous studies of the genetics of facial abnormalities and, more recently, single nucleotide polymorphism (SNP) genome-wide association studies (GWASs) of normal facial variation, little is known about the role of genetic structural variation in determining facial shape. In a sample of Bantu African children, we found that only 9% of common copy number variants (CNVs) and 10-kb CNV analysis windows are well tagged by SNPs (r2 ≥ 0.8), indicating that associations with our internally called CNVs were not captured by previous SNP-based GWASs. Here, we present a GWAS and gene set analysis of the relationship between normal facial variation and CNVs in a sample of Bantu African children. We report the top five regions, which had p values ≤ 9.35 × 10−6 and find nominal evidence of independent CNV association (p < 0.05) in three regions previously identified in SNP-based GWASs. The CNV region with strongest association (p = 1.16 × 10−6, 55 losses and seven gains) contains NFATC1, which has been linked to facial morphogenesis and Cherubism, a syndrome involving abnormal lower facial development. Genomic loss in the region is associated with smaller average lower facial depth. Importantly, new loci identified here were not identified in a SNP-based GWAS, suggesting that CNVs are likely involved in determining facial shape variation. Given the plethora of SNP-based GWASs, calling CNVs from existing data may be a relatively inexpensive way to aid in the study of complex traits. |
| first_indexed | 2024-12-18T05:09:58Z |
| format | Article |
| id | doaj.art-33d2bde0be194f3296718f47b89ac036 |
| institution | Directory Open Access Journal |
| issn | 2666-2477 |
| language | English |
| last_indexed | 2024-12-18T05:09:58Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | HGG Advances |
| spelling | doaj.art-33d2bde0be194f3296718f47b89ac0362022-12-21T21:19:54ZengElsevierHGG Advances2666-24772022-01-0131100082Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu AfricansMegan Null0Feyza Yilmaz1David Astling2Hung-Chun Yu3Joanne B. Cole4Benedikt Hallgrímsson5Stephanie A. Santorico6Richard A. Spritz7Tamim H. Shaikh8Audrey E. Hendricks9Mathematical and Statistical Sciences, University of Colorado Denver, Denver, CO, USA; Department of Mathematics and Physical Sciences, The College of Idaho, Caldwell, ID 83605, USADepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Integrative Biology, University of Colorado Denver, Denver, CO 80204, USADepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Human Medical Genetics and Genomics Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Cell Biology & Anatomy, Alberta Children Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, CanadaMathematical and Statistical Sciences, University of Colorado Denver, Denver, CO, USA; Human Medical Genetics and Genomics Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO 80045, USADepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Human Medical Genetics and Genomics Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Human Medical Genetics and Genomics Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Corresponding authorMathematical and Statistical Sciences, University of Colorado Denver, Denver, CO, USA; Human Medical Genetics and Genomics Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO 80045, USA; Corresponding authorSimilarity in facial characteristics between relatives suggests a strong genetic component underlies facial variation. While there have been numerous studies of the genetics of facial abnormalities and, more recently, single nucleotide polymorphism (SNP) genome-wide association studies (GWASs) of normal facial variation, little is known about the role of genetic structural variation in determining facial shape. In a sample of Bantu African children, we found that only 9% of common copy number variants (CNVs) and 10-kb CNV analysis windows are well tagged by SNPs (r2 ≥ 0.8), indicating that associations with our internally called CNVs were not captured by previous SNP-based GWASs. Here, we present a GWAS and gene set analysis of the relationship between normal facial variation and CNVs in a sample of Bantu African children. We report the top five regions, which had p values ≤ 9.35 × 10−6 and find nominal evidence of independent CNV association (p < 0.05) in three regions previously identified in SNP-based GWASs. The CNV region with strongest association (p = 1.16 × 10−6, 55 losses and seven gains) contains NFATC1, which has been linked to facial morphogenesis and Cherubism, a syndrome involving abnormal lower facial development. Genomic loss in the region is associated with smaller average lower facial depth. Importantly, new loci identified here were not identified in a SNP-based GWAS, suggesting that CNVs are likely involved in determining facial shape variation. Given the plethora of SNP-based GWASs, calling CNVs from existing data may be a relatively inexpensive way to aid in the study of complex traits.http://www.sciencedirect.com/science/article/pii/S2666247721000634copy number variantsnormal facial variationface shapeCNVAfricanBantu |
| spellingShingle | Megan Null Feyza Yilmaz David Astling Hung-Chun Yu Joanne B. Cole Benedikt Hallgrímsson Stephanie A. Santorico Richard A. Spritz Tamim H. Shaikh Audrey E. Hendricks Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu Africans HGG Advances copy number variants normal facial variation face shape CNV African Bantu |
| title | Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu Africans |
| title_full | Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu Africans |
| title_fullStr | Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu Africans |
| title_full_unstemmed | Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu Africans |
| title_short | Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu Africans |
| title_sort | genome wide analysis of copy number variants and normal facial variation in a large cohort of bantu africans |
| topic | copy number variants normal facial variation face shape CNV African Bantu |
| url | http://www.sciencedirect.com/science/article/pii/S2666247721000634 |
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