Integrating GWAS and eQTL to predict genes and pathways for non-syndromic cleft lip with or without palate
- 1 October 2021
- journal article
- research article
- Published by Wiley in Oral Diseases
- Vol. 27 (7), 1747-1754
- https://doi.org/10.1111/odi.13699
Abstract
Objective To explore susceptibility genes and pathways for non-syndromic cleft lip with or without cleft palate (NSCL/P). Materials and methods Two genome-wide association studies (GWAS) datasets, including 858 NSCL/P cases and 1,248 controls, were integrated with expression quantitative trait loci (eQTL) dataset identified by Genotype-Tissue Expression (GTEx) project in whole-blood samples. The expression of the candidate genes in mouse orofacial development was inquired from FaceBase. Protein-protein interaction (PPI) network was visualized to identify protein functions. Go and KEGG pathway analyses were performed to explore the underlying risk pathways. Results A total of 233 eQTL single-nucleotide polymorphisms (SNPs) in 432 candidate genes were identified to be associated with the risk of NSCL/P. One hundred and eighty-three susceptible genes were expressed in mouse orofacial development according to FaceBase. PPI network analysis highlighted that these genes involved in ubiquitin-mediated proteolysis (KCTD7, ASB1, UBOX5, ANAPC4) and DNA synthesis (XRCC3, RFC3, KAT5, RHNO1) were associated with the risk of NSCL/P. GO and KEGG pathway analyses revealed that the fatty acid metabolism pathway (ACADL, HSD17B12, ACSL5, PPT1, MCAT) played an important role in the development of NSCL/P. Conclusions Our results identified novel susceptibility genes and pathways associated with the development of NSCL/P.Keywords
Funding Information
- National Natural Science Foundation of China (81970969, 81830031, 81570959)
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