Genome‐wide meta‐analyses identify five new risk loci for nonsyndromic orofacial clefts in the Chinese Han population
Abstract Background Nonsyndromic orofacial clefts (NSOFCs) are the most common craniofacial birth malformations in humans and are generally classified as nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO). Genome‐wide association studies (GWASs) o...
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| Format: | Article |
| Jezik: | English |
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Wiley
2023-10-01
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| Serija: | Molecular Genetics & Genomic Medicine |
| Teme: | |
| Online dostop: | https://doi.org/10.1002/mgg3.2226 |
| _version_ | 1827795037399810048 |
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| author | Yafen Yu Qi Zhen Weiwei Chen Yanqin Yu Zhuo Li Yirui Wang Wencheng Fan Sihan Luo Daiyue Wang Yuanming Bai Zhuan Bian Miao He Liangdan Sun |
| author_facet | Yafen Yu Qi Zhen Weiwei Chen Yanqin Yu Zhuo Li Yirui Wang Wencheng Fan Sihan Luo Daiyue Wang Yuanming Bai Zhuan Bian Miao He Liangdan Sun |
| author_sort | Yafen Yu |
| collection | DOAJ |
| description | Abstract Background Nonsyndromic orofacial clefts (NSOFCs) are the most common craniofacial birth malformations in humans and are generally classified as nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO). Genome‐wide association studies (GWASs) of NSOFCs have demonstrated multiple risk loci and candidate genes; however, published risk factors are able to explain only a small fraction of the observed NSOFCs heritability. Methods Here, we performed GWASs of 1615 NSCPO cases and 2340 controls, and then conducted genome‐wide meta‐analyses of NSOFCs, totaling 6812 NSCL/P cases, 2614 NSCPO cases, and 19,165 controls from the Chinese Han population. Results We identify 47 risk loci with genome‐wide pmeta‐value <5.0 × 10−8, 5 risk loci (1p32.1, 3p14.1, 3p14.3, 3p21.31, and 13q22.1) of which are new. All of the 47 susceptibility loci conjointly account for 44.12% of the NSOFCs’ heritability in the Chinese Han population. Conclusion Our results improve the comprehending of genetic susceptibility to NSOFCs and provide new views into the genetic etiology of craniofacial anomalies. |
| first_indexed | 2024-03-11T18:42:30Z |
| format | Article |
| id | doaj.art-35ec4b3d8ba045379712c99479f96fce |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-11T18:42:30Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-35ec4b3d8ba045379712c99479f96fce2023-10-12T08:38:42ZengWileyMolecular Genetics & Genomic Medicine2324-92692023-10-011110n/an/a10.1002/mgg3.2226Genome‐wide meta‐analyses identify five new risk loci for nonsyndromic orofacial clefts in the Chinese Han populationYafen Yu0Qi Zhen1Weiwei Chen2Yanqin Yu3Zhuo Li4Yirui Wang5Wencheng Fan6Sihan Luo7Daiyue Wang8Yuanming Bai9Zhuan Bian10Miao He11Liangdan Sun12Department of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‐MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology Wuhan University Wuhan ChinaDepartment of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‐MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology Wuhan University Wuhan ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‐MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology Wuhan University Wuhan ChinaDepartment of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei ChinaAbstract Background Nonsyndromic orofacial clefts (NSOFCs) are the most common craniofacial birth malformations in humans and are generally classified as nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO). Genome‐wide association studies (GWASs) of NSOFCs have demonstrated multiple risk loci and candidate genes; however, published risk factors are able to explain only a small fraction of the observed NSOFCs heritability. Methods Here, we performed GWASs of 1615 NSCPO cases and 2340 controls, and then conducted genome‐wide meta‐analyses of NSOFCs, totaling 6812 NSCL/P cases, 2614 NSCPO cases, and 19,165 controls from the Chinese Han population. Results We identify 47 risk loci with genome‐wide pmeta‐value <5.0 × 10−8, 5 risk loci (1p32.1, 3p14.1, 3p14.3, 3p21.31, and 13q22.1) of which are new. All of the 47 susceptibility loci conjointly account for 44.12% of the NSOFCs’ heritability in the Chinese Han population. Conclusion Our results improve the comprehending of genetic susceptibility to NSOFCs and provide new views into the genetic etiology of craniofacial anomalies.https://doi.org/10.1002/mgg3.2226common variantsgenetic risk locigenome‐wide association studyorofacial cleftssusceptibility |
| spellingShingle | Yafen Yu Qi Zhen Weiwei Chen Yanqin Yu Zhuo Li Yirui Wang Wencheng Fan Sihan Luo Daiyue Wang Yuanming Bai Zhuan Bian Miao He Liangdan Sun Genome‐wide meta‐analyses identify five new risk loci for nonsyndromic orofacial clefts in the Chinese Han population Molecular Genetics & Genomic Medicine common variants genetic risk loci genome‐wide association study orofacial clefts susceptibility |
| title | Genome‐wide meta‐analyses identify five new risk loci for nonsyndromic orofacial clefts in the Chinese Han population |
| title_full | Genome‐wide meta‐analyses identify five new risk loci for nonsyndromic orofacial clefts in the Chinese Han population |
| title_fullStr | Genome‐wide meta‐analyses identify five new risk loci for nonsyndromic orofacial clefts in the Chinese Han population |
| title_full_unstemmed | Genome‐wide meta‐analyses identify five new risk loci for nonsyndromic orofacial clefts in the Chinese Han population |
| title_short | Genome‐wide meta‐analyses identify five new risk loci for nonsyndromic orofacial clefts in the Chinese Han population |
| title_sort | genome wide meta analyses identify five new risk loci for nonsyndromic orofacial clefts in the chinese han population |
| topic | common variants genetic risk loci genome‐wide association study orofacial clefts susceptibility |
| url | https://doi.org/10.1002/mgg3.2226 |
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