P Wang1,2, T Wu1,3, H Schwender4, H Wang1, B Shi5, Z Q Wang1, Y Yuan1, D J Liu1, M Y Wang1, J Li6, Z B Zhou7, H P Zhu7, T H Beaty8. 1. School of Public Health, Peking University, Beijing, China. 2. Department of Statistics and Information, Beijing Center for Disease Prevention and Control & Beijing Research Center for Preventive Medicine, Beijing, China. 3. Key Laboratory of Reproductive Health, Ministry of Health, Beijing, China. 4. Mathematical Institute, Heinrich Heine University Duesseldorf, Duesseldorf, Germany. 5. State Key Laboratory of Oral Disease, West China School of Stomatology, Sichuan University, Chengdu, China. 6. Pediatric Dentistry, Peking University School of Stomatology, Beijing, China. 7. Oral and Maxillofacial Surgery, Peking University School of Stomatology, Beijing, China. 8. School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Abstract
OBJECTIVE: Little consistent evidence is available for the association between the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P) and any of the individual genes in the folate/homocysteine metabolic pathway. We investigated the genes in the folate pathway to further clarify its potential influence on the risk of NSCL/P considering gene-gene (G×G) interaction. SUBJECTS AND METHODS: We selected markers in 18 genes from the pathway and applied Cordell's method to test for G×G interaction using 1,908 NSCL/P case-parent trios ascertained in an international consortium where a genomewide association study (GWAS) of oral clefts was conducted. RESULTS: We found intriguing signals among Asian and European ancestry groups for G×G interaction between markers in betaine-homocysteine methyltransferase gene (BHMT/BHMT2) and dimethylglycine dehydrogenase gene (DMGDH) attaining genomewide significance. In the pooled data, the top significant interaction was found between rs13158309 (BHMT) and rs10514154 (DMGDH, p = 1.45 × 10-12 ). CONCLUSIONS: Our study illustrated the importance of taking into account potential G×G interaction for genetic association analysis in NSCL/P, and this study suggested both BHMT/BHMT2 and DMGDH should be considered as candidate genes for NSCL/P in future studies.
OBJECTIVE: Little consistent evidence is available for the association between the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P) and any of the individual genes in the folate/homocysteine metabolic pathway. We investigated the genes in the folate pathway to further clarify its potential influence on the risk of NSCL/P considering gene-gene (G×G) interaction. SUBJECTS AND METHODS: We selected markers in 18 genes from the pathway and applied Cordell's method to test for G×G interaction using 1,908 NSCL/P case-parent trios ascertained in an international consortium where a genomewide association study (GWAS) of oral clefts was conducted. RESULTS: We found intriguing signals among Asian and European ancestry groups for G×G interaction between markers in betaine-homocysteine methyltransferase gene (BHMT/BHMT2) and dimethylglycine dehydrogenase gene (DMGDH) attaining genomewide significance. In the pooled data, the top significant interaction was found between rs13158309 (BHMT) and rs10514154 (DMGDH, p = 1.45 × 10-12 ). CONCLUSIONS: Our study illustrated the importance of taking into account potential G×G interaction for genetic association analysis in NSCL/P, and this study suggested both BHMT/BHMT2 and DMGDH should be considered as candidate genes for NSCL/P in future studies.
Authors: Kurt Reynolds; Shuwen Zhang; Bo Sun; Michael A Garland; Yu Ji; Chengji J Zhou Journal: Birth Defects Res Date: 2020-07-15 Impact factor: 2.344
Authors: Carlos Salamanca; Patricio González-Hormazábal; Andrea S Recabarren; Pamela A Recabarren; Roberto Pantoja; Noemi Leiva; Rosa Pardo; José Suazo Journal: Pediatr Res Date: 2020-06-03 Impact factor: 3.756