Mendelian randomization analysis identified genes potentially pleiotropically associated with periodontitis

Feng Wang; Di Liu; Yong Zhuang; Bowen Feng; Wenjin Lu; Jingyun Yang; Guanghui Zhuang

doi:10.1016/j.sjbs.2021.04.028

Mendelian randomization analysis identified genes potentially pleiotropically associated with periodontitis

Saudi J Biol Sci. 2021 Jul;28(7):4089-4095. doi: 10.1016/j.sjbs.2021.04.028. Epub 2021 Apr 16.

Authors

Feng Wang¹, Di Liu², Yong Zhuang³, Bowen Feng⁴, Wenjin Lu⁵, Jingyun Yang^{6

7}, Guanghui Zhuang¹

Affiliations

¹ Department of Stomatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
² Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China.
³ Department of Stomatology, Dalian Medical University, Dalian, Liaoning, China.
⁴ Odette School of Business, University of Windsor, Windsor, ON, Canada.
⁵ Department of Mathematics, University College London, London, United Kingdom.
⁶ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
⁷ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.

Abstract

Objective: To prioritize genes that were pleiotropically or potentially causally associated with periodontitis.

Methods: We applied the summary data-based Mendelian randomization (SMR) method integrating genome-wide association study (GWAS) for periodontitis and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with periodontitis. We performed separate SMR analysis using CAGE eQTL data and GTEx eQTL data. SMR analysis were done for participants of European and East Asian ancestries, separately.

Results: We identified multiple genes showing pleiotropic association with periodontitis in participants of European ancestry and participants of East Asian ancestry. PDCD2 (corresponding probe: ILMN_1758915) was the top hit showing pleotropic association with periodontitis in the participants of European ancestry using CAGE eQTL data, and BX093763 (corresponding probe: ILMN_1899903) and AC104135.3 (corresponding probe: ENSG00000204792.2) were the top hits in the participants of East Asian ancestry using CAGE eQTL data and GTEx eQTL data, respectively.

Conclusion: We identified multiple genes that may be involved in the pathogenesis of periodontitis in participants of European ancestry and participants of East Asian ancestry. Our findings provided important leads to a better understanding of the mechanisms underlying periodontitis and revealed potential therapeutic targets for the effective treatment of periodontitis.

Keywords: Expression quantitative trait loci; GO, Gene ontology; GWAS, Genome-wide association studies; HEIDI, Heterogeneity in dependent instruments; IVs, Instrumental variables; KEGG, Kyoto Encyclopedia of Genes and Genomes; LD, Linkage disequilibrium; MR, Mendelian randomization; Periodontitis; Pleotropic association; SMR, Summary data-based Mendelian randomization; Summary Mendelian randomization; eQTL, expression quantitative trait loci.

Abstract

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