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. 2021 Oct;27(7):1747-1754.
doi: 10.1111/odi.13699. Epub 2020 Dec 14.

Integrating GWAS and eQTL to predict genes and pathways for non-syndromic cleft lip with or without palate

Jing Yang  1   2 , Xin Yu  1   2 , Guirong Zhu  1   2 , Ruimin Wang  1 , Shu Lou  1   2 , Weihao Zhu  1   2 , Chengyi Fu  1   2 , Jinsuo Liu  3 , Liwen Fan  1   2 , Dandan Li  1   2 , Qinghua Shao  1   2 , Lan Ma  1 , Lin Wang  1   2   4 , Zhendong Wang  1   2 , Yongchu Pan  1   2   4
Affiliations

Integrating GWAS and eQTL to predict genes and pathways for non-syndromic cleft lip with or without palate

Jing Yang et al. Oral Dis. 2021 Oct.

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: expression quantitative trait loci; genes; genome-wide association study; non-syndromic cleft lip with or without cleft palate; pathway.

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