Expression Quantitative Trait Locus Study of Non-Syndromic Cleft Lip with or without Cleft Palate GWAS Variants in Lip Tissues
Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a complex disease with a strong genetic component. More than 40 loci have been identified to be associated with the risk of NSCL/P by genome-wide association studies (GWASs), but the majority of these variants are mapped to non-coding...
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MDPI AG
2022-10-01
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| author | Xiaofeng Li Yu Tian Ling Qiu Shu Lou Guirong Zhu Yue Gao Lan Ma Yongchu Pan |
| author_facet | Xiaofeng Li Yu Tian Ling Qiu Shu Lou Guirong Zhu Yue Gao Lan Ma Yongchu Pan |
| author_sort | Xiaofeng Li |
| collection | DOAJ |
| description | Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a complex disease with a strong genetic component. More than 40 loci have been identified to be associated with the risk of NSCL/P by genome-wide association studies (GWASs), but the majority of these variants are mapped to non-coding regions of the genome. Expression quantitative trait locus (eQTL) studies have increasingly been integrated with GWASs to identify target genes for these non-coding variants. In this study, we generated a unique, lip-specific eQTL dataset from 40 NSCL/P patients. A total of 5158 eQTL SNPs (eSNPs) -689 eQTL genes were identified after multiple corrections. Then, we integrated nominal eQTL SNPs with NSCL/P risk SNPs and identified 243 variants associated with the expression of 18 genes in lip tissues. Functional annotation analysis indicated that these risk eSNPs were significantly enriched in transcription regulation and chromatin open regions on the genome. These susceptible genes were enriched in cell fate determination, the pluripotency of stem cells, and Wnt signaling pathways. Finally, 8 of the 18 susceptible genes were differentially expressed in NSCL/P case-control studies. In summary, we have generated a unique lip-specific eQTL resource and identified multiple associations for NSCL/P risk loci, which should inform functional studies of NSCL/P biology. |
| first_indexed | 2024-03-09T20:28:50Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:28:50Z |
| publishDate | 2022-10-01 |
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| spelling | doaj.art-1e567d1caa014c1f9df9c4f5b34f6bf22023-11-23T23:28:33ZengMDPI AGCells2073-44092022-10-011120328110.3390/cells11203281Expression Quantitative Trait Locus Study of Non-Syndromic Cleft Lip with or without Cleft Palate GWAS Variants in Lip TissuesXiaofeng Li0Yu Tian1Ling Qiu2Shu Lou3Guirong Zhu4Yue Gao5Lan Ma6Yongchu Pan7Jiangsu Province Key Laboratory of Oral Diseases, Nanjing 210000, ChinaJiangsu Province Key Laboratory of Oral Diseases, Nanjing 210000, ChinaJiangsu Province Key Laboratory of Oral Diseases, Nanjing 210000, ChinaJiangsu Province Key Laboratory of Oral Diseases, Nanjing 210000, ChinaJiangsu Province Key Laboratory of Oral Diseases, Nanjing 210000, ChinaJiangsu Province Key Laboratory of Oral Diseases, Nanjing 210000, ChinaJiangsu Province Key Laboratory of Oral Diseases, Nanjing 210000, ChinaJiangsu Province Key Laboratory of Oral Diseases, Nanjing 210000, ChinaNon-syndromic cleft lip with or without cleft palate (NSCL/P) is a complex disease with a strong genetic component. More than 40 loci have been identified to be associated with the risk of NSCL/P by genome-wide association studies (GWASs), but the majority of these variants are mapped to non-coding regions of the genome. Expression quantitative trait locus (eQTL) studies have increasingly been integrated with GWASs to identify target genes for these non-coding variants. In this study, we generated a unique, lip-specific eQTL dataset from 40 NSCL/P patients. A total of 5158 eQTL SNPs (eSNPs) -689 eQTL genes were identified after multiple corrections. Then, we integrated nominal eQTL SNPs with NSCL/P risk SNPs and identified 243 variants associated with the expression of 18 genes in lip tissues. Functional annotation analysis indicated that these risk eSNPs were significantly enriched in transcription regulation and chromatin open regions on the genome. These susceptible genes were enriched in cell fate determination, the pluripotency of stem cells, and Wnt signaling pathways. Finally, 8 of the 18 susceptible genes were differentially expressed in NSCL/P case-control studies. In summary, we have generated a unique lip-specific eQTL resource and identified multiple associations for NSCL/P risk loci, which should inform functional studies of NSCL/P biology.https://www.mdpi.com/2073-4409/11/20/3281cleft lipcleft palategenetic variationeQTLassociation study |
| spellingShingle | Xiaofeng Li Yu Tian Ling Qiu Shu Lou Guirong Zhu Yue Gao Lan Ma Yongchu Pan Expression Quantitative Trait Locus Study of Non-Syndromic Cleft Lip with or without Cleft Palate GWAS Variants in Lip Tissues Cells cleft lip cleft palate genetic variation eQTL association study |
| title | Expression Quantitative Trait Locus Study of Non-Syndromic Cleft Lip with or without Cleft Palate GWAS Variants in Lip Tissues |
| title_full | Expression Quantitative Trait Locus Study of Non-Syndromic Cleft Lip with or without Cleft Palate GWAS Variants in Lip Tissues |
| title_fullStr | Expression Quantitative Trait Locus Study of Non-Syndromic Cleft Lip with or without Cleft Palate GWAS Variants in Lip Tissues |
| title_full_unstemmed | Expression Quantitative Trait Locus Study of Non-Syndromic Cleft Lip with or without Cleft Palate GWAS Variants in Lip Tissues |
| title_short | Expression Quantitative Trait Locus Study of Non-Syndromic Cleft Lip with or without Cleft Palate GWAS Variants in Lip Tissues |
| title_sort | expression quantitative trait locus study of non syndromic cleft lip with or without cleft palate gwas variants in lip tissues |
| topic | cleft lip cleft palate genetic variation eQTL association study |
| url | https://www.mdpi.com/2073-4409/11/20/3281 |
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