Genetic associations and parent-of-origin effects of PVRL1 in non-syndromic cleft lip with or without cleft palate across multiple ethnic populations
OBJECTIVES This study investigated the associations of PVRL1 gene variants with non-syndromic cleft lip with or without cleft palate (NSCL/P) by evaluating transmission distortion and parent-of-origin (POO) effects in multiple ethnic populations. METHODS We conducted allelic and genotypic transmissi...
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Korean Society of Epidemiology
2024-08-01
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| Series: | Epidemiology and Health |
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| Online Access: | http://www.e-epih.org/upload/pdf/epih-46-e2024069.pdf |
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| author | Ji Wan Park Geon Kang Seung-Hak Baek Young Ho Kim |
| author_facet | Ji Wan Park Geon Kang Seung-Hak Baek Young Ho Kim |
| author_sort | Ji Wan Park |
| collection | DOAJ |
| description | OBJECTIVES This study investigated the associations of PVRL1 gene variants with non-syndromic cleft lip with or without cleft palate (NSCL/P) by evaluating transmission distortion and parent-of-origin (POO) effects in multiple ethnic populations. METHODS We conducted allelic and genotypic transmission disequilibrium tests (TDT) on 10 single-nucleotide variants (SNVs) in PVRL1 using data from 142 Korean families with an affected child. POO effects were analyzed using the POO likelihood ratio test, comparing transmission rates of maternally and paternally inherited alleles. To assess generalizability and ethnic heterogeneity, we compared results from Korean families with data from the Center for Craniofacial and Dental Genetics, which included 2,226 individuals from 497 European and 245 Asian trios. RESULTS TDT analysis identified significant over-transmission of the rs7940667 (G361V) C allele in Korean families (p=0.007), a finding replicated in both Asian (p=6.5×10-7) and European families (p=1.6×10-10). Eight SNVs showed strong TDT evidence in larger Asian and European datasets after multiple comparison corrections (p<0.0073). Of these, 4 SNVs (rs7940667, rs7103685, rs7129848, and rs4409845) showed particularly robust association (p<5×10-8). POO analysis revealed significant maternal over-transmission of the rs10790330-A allele in Korean families (p=0.044). This finding was replicated in European families (p=9.0×10-4). Additionally, 3 other SNVs, rs7129848 (p=0.001) and the linked SNVs rs3935406 and rs10892434 (p=0.025), exhibited maternal over-transmission in the validation datasets. CONCLUSIONS Our findings provide robust evidence supporting the associations of PVRL1 variants with NSCL/P susceptibility. Further research is necessary to explore the potential clinical applications of these findings. |
| format | Article |
| id | doaj-art-aff0e134df47427db85f6e3b0617e69c |
| institution | DOAJ |
| issn | 2092-7193 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Korean Society of Epidemiology |
| record_format | Article |
| series | Epidemiology and Health |
| spelling | doaj-art-aff0e134df47427db85f6e3b0617e69c2025-08-20T03:12:36ZengKorean Society of EpidemiologyEpidemiology and Health2092-71932024-08-014610.4178/epih.e20240691535Genetic associations and parent-of-origin effects of PVRL1 in non-syndromic cleft lip with or without cleft palate across multiple ethnic populationsJi Wan Park0Geon Kang1Seung-Hak Baek2Young Ho Kim3 Department of Medical Genetics, Hallym University College of Medicine, Chuncheon, Korea Department of Medical Genetics, Hallym University College of Medicine, Chuncheon, Korea Department of Orthodontics, Seoul National University School of Dentistry, Seoul, Korea Department of Orthodontics, Institute of Oral Health Science, Ajou University School of Medicine, Suwon, KoreaOBJECTIVES This study investigated the associations of PVRL1 gene variants with non-syndromic cleft lip with or without cleft palate (NSCL/P) by evaluating transmission distortion and parent-of-origin (POO) effects in multiple ethnic populations. METHODS We conducted allelic and genotypic transmission disequilibrium tests (TDT) on 10 single-nucleotide variants (SNVs) in PVRL1 using data from 142 Korean families with an affected child. POO effects were analyzed using the POO likelihood ratio test, comparing transmission rates of maternally and paternally inherited alleles. To assess generalizability and ethnic heterogeneity, we compared results from Korean families with data from the Center for Craniofacial and Dental Genetics, which included 2,226 individuals from 497 European and 245 Asian trios. RESULTS TDT analysis identified significant over-transmission of the rs7940667 (G361V) C allele in Korean families (p=0.007), a finding replicated in both Asian (p=6.5×10-7) and European families (p=1.6×10-10). Eight SNVs showed strong TDT evidence in larger Asian and European datasets after multiple comparison corrections (p<0.0073). Of these, 4 SNVs (rs7940667, rs7103685, rs7129848, and rs4409845) showed particularly robust association (p<5×10-8). POO analysis revealed significant maternal over-transmission of the rs10790330-A allele in Korean families (p=0.044). This finding was replicated in European families (p=9.0×10-4). Additionally, 3 other SNVs, rs7129848 (p=0.001) and the linked SNVs rs3935406 and rs10892434 (p=0.025), exhibited maternal over-transmission in the validation datasets. CONCLUSIONS Our findings provide robust evidence supporting the associations of PVRL1 variants with NSCL/P susceptibility. Further research is necessary to explore the potential clinical applications of these findings.http://www.e-epih.org/upload/pdf/epih-46-e2024069.pdfcase-parent trio designnonsyndromic cleft lip with or without cleft palateparent-of-origin effecthuman poliovirus receptor related 1transmission disequilibrium test |
| spellingShingle | Ji Wan Park Geon Kang Seung-Hak Baek Young Ho Kim Genetic associations and parent-of-origin effects of PVRL1 in non-syndromic cleft lip with or without cleft palate across multiple ethnic populations Epidemiology and Health case-parent trio design nonsyndromic cleft lip with or without cleft palate parent-of-origin effect human poliovirus receptor related 1 transmission disequilibrium test |
| title | Genetic associations and parent-of-origin effects of PVRL1 in non-syndromic cleft lip with or without cleft palate across multiple ethnic populations |
| title_full | Genetic associations and parent-of-origin effects of PVRL1 in non-syndromic cleft lip with or without cleft palate across multiple ethnic populations |
| title_fullStr | Genetic associations and parent-of-origin effects of PVRL1 in non-syndromic cleft lip with or without cleft palate across multiple ethnic populations |
| title_full_unstemmed | Genetic associations and parent-of-origin effects of PVRL1 in non-syndromic cleft lip with or without cleft palate across multiple ethnic populations |
| title_short | Genetic associations and parent-of-origin effects of PVRL1 in non-syndromic cleft lip with or without cleft palate across multiple ethnic populations |
| title_sort | genetic associations and parent of origin effects of pvrl1 in non syndromic cleft lip with or without cleft palate across multiple ethnic populations |
| topic | case-parent trio design nonsyndromic cleft lip with or without cleft palate parent-of-origin effect human poliovirus receptor related 1 transmission disequilibrium test |
| url | http://www.e-epih.org/upload/pdf/epih-46-e2024069.pdf |
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