The causal association between osteoporosis and periodontitis: A two-sample Mendelian randomization study

doi:10.3877/cma.j.issn.1674-1366.2023.04.010

Abstract

Abstract:

Objective

To explore the causal relationship between osteoporosis and periodontitis with Mendelian randomization (MR) analysis.

Methods

Mutually independent SNPs associated with osteoporosis (exposure) were screened out from two Genome-wide association study (GWAS) databases (GEFOS, European, n = 142 487; BBJ, East Asian, n = 212 453). The SNP data on periodontitis (outcome) were obtained from another two GWAS databases and relevant SNPs corresponding to the exposure were selected as instrumental variables. Two-sample MR analysis was conducted with methods of inverse variance weighted (IVW), MR-Egger regression and weighted median. The causal association between osteoporosis and periodontitis was estimated with odds ratios.

Results

Totally 207 and 7 SNPs were screened out from European and East Asian populations, respectively. IVW did not support a causal relationship between osteoporosis and periodontitis (European: odds ratio = 0.964, P = 0.281; East Asian: odds ratio = 0.892, P = 0.090). The intercept of MR-Egger regression was unequal to zero, suggesting there was no genetic pleiotropy (intercept = 0.000 3, P = 0.909). Specific SNP was not found with leave-one-out analysis.

Conclusion

MR study does not support a causal association between osteoporosis and periodontitis in European and East Asian populations.

Key words: Periodontitis, Bone mineral density, Osteoporosis, Mendelian randomization study

Yueqi Chen, Rui Luo, Han Xiang, Yongyan Yu, Ting Yu. The causal association between osteoporosis and periodontitis: A two-sample Mendelian randomization study[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2023, 17(04): 292-298.

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Figures/Tables 10

References 8

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人群	变量	下载文件名	样本量（人）	SNP位点（个）	数据库	缩写	年份
欧洲^a	骨密度	UKBB eBMD GWAS Data Release 2017	142 487	17 166 351	http://www.gefos.org/?q=content/ukbb-ebmd-gwas-data-release-2017	GEFOS	2017
	牙周炎	GWAS summary statistics for dental caries and periodontitis	45 563	461 031	https://data.bris.ac.uk/data/dataset/2j2rqgzedxlq02oqbb4vmycnc2	GLIDE	2019
东亚^b	骨质疏松症	Osteoporosis	212 453	-	https://jenger.riken.jp/result	BBJ	2021
	牙周病	Periodontal disease	178 726	-	https://pheweb.jp/pheno/Periodontal_Disease	BBJ	2021

人群	变量	下载文件名	样本量（人）	SNP位点（个）	数据库	缩写	年份
欧洲^a	骨密度	UKBB eBMD GWAS Data Release 2017	142 487	17 166 351	http://www.gefos.org/?q=content/ukbb-ebmd-gwas-data-release-2017	GEFOS	2017
	牙周炎	GWAS summary statistics for dental caries and periodontitis	45 563	461 031	https://data.bris.ac.uk/data/dataset/2j2rqgzedxlq02oqbb4vmycnc2	GLIDE	2019
东亚^b	骨质疏松症	Osteoporosis	212 453	-	https://jenger.riken.jp/result	BBJ	2021
	牙周病	Periodontal disease	178 726	-	https://pheweb.jp/pheno/Periodontal_Disease	BBJ	2021

人群	SNP	chr	EA	OA	EAF	骨质疏松症			牙周炎			R²	F值
人群	SNP	chr	EA	OA	EAF	β	SE	P值	β	SE	P值	R²	F值
欧洲	rs10022648	4	A	G	0.614	0.023	0.003	5.45 × 10^-11	-0.002	0.015	0.899	0.000 25	37.1
	rs10130587	14	G	C	0.594	-0.063	0.004	3.53 × 10^-69	0.012	0.016	0.472	0.001 91	286.7
	rs1013339	22	C	T	0.667	0.021	0.004	2.09 × 10^-9	0.009	0.015	0.566	0.000 21	30.8
	rs10139279	14	G	A	0.659	0.042	0.004	1.40 × 10^-32	-0.012	0.016	0.466	0.000 81	121.3
	……
	rs9327301	5	G	A	0.743	0.024	0.004	6.29 × 10^-10	0.008	0.018	0.670	0.000 22	32.6
	rs884205	18	A	C	0.249	-0.033	0.004	2.76 × 10^-17	-0.005	0.018	0.800	0.000 41	61.9
	rs9524200	13	A	G	0.052	-0.046	0.008	2.46 × 10^-9	0.009	0.033	0.775	0.000 21	30.8
	rs9606139	22	G	A	0.890	0.114	0.006	1.06 × 10^-93	0.042	0.030	0.170	0.002 53	381.0
	合计^a											0.000 58	87.7
东亚	rs114207218	1	G	T	0.114	-0.138	0.030	4.47 × 10^-6	-0.025	0.026	0.340	0.003 83	817.8
	rs12525228	6	C	T	0.804	0.119	0.024	9.03 × 10^-7	-0.009	0.021	0.681	0.004 49	958.5
	rs1576901	9	A	T	0.714	0.096	0.020	1.47 × 10^-6	0.032	0.017	0.064	0.003 80	811.1
	rs2864700	1	C	T	0.762	0.144	0.028	2.23 × 10^-7	-0.044	0.023	0.050	0.007 55	1 615.3
	rs4635671	3	G	T	0.213	-0.103	0.022	3.41 × 10^-6	0.031	0.019	0.103	0.003 54	755.2
	rs73573476	19	G	A	0.739	0.238	0.050	1.91 × 10^-6	0.011	0.041	0.795	0.021 77	4 728.3
	rs77430782	19	C	T	0.729	0.101	0.022	4.86 × 10^-6	-0.019	0.019	0.318	0.004 01	855.6
	rs948367	11	C	T	0.175	-0.087	0.019	4.14 × 10^-6	0.008	0.016	0.629	0.002 19	465.9
	合计^a											0.006 40	1 376.0

人群	SNP	chr	EA	OA	EAF	骨质疏松症			牙周炎			R²	F值
人群	SNP	chr	EA	OA	EAF	β	SE	P值	β	SE	P值	R²	F值
欧洲	rs10022648	4	A	G	0.614	0.023	0.003	5.45 × 10^-11	-0.002	0.015	0.899	0.000 25	37.1
	rs10130587	14	G	C	0.594	-0.063	0.004	3.53 × 10^-69	0.012	0.016	0.472	0.001 91	286.7
	rs1013339	22	C	T	0.667	0.021	0.004	2.09 × 10^-9	0.009	0.015	0.566	0.000 21	30.8
	rs10139279	14	G	A	0.659	0.042	0.004	1.40 × 10^-32	-0.012	0.016	0.466	0.000 81	121.3
	……
	rs9327301	5	G	A	0.743	0.024	0.004	6.29 × 10^-10	0.008	0.018	0.670	0.000 22	32.6
	rs884205	18	A	C	0.249	-0.033	0.004	2.76 × 10^-17	-0.005	0.018	0.800	0.000 41	61.9
	rs9524200	13	A	G	0.052	-0.046	0.008	2.46 × 10^-9	0.009	0.033	0.775	0.000 21	30.8
	rs9606139	22	G	A	0.890	0.114	0.006	1.06 × 10^-93	0.042	0.030	0.170	0.002 53	381.0
	合计^a											0.000 58	87.7
东亚	rs114207218	1	G	T	0.114	-0.138	0.030	4.47 × 10^-6	-0.025	0.026	0.340	0.003 83	817.8
	rs12525228	6	C	T	0.804	0.119	0.024	9.03 × 10^-7	-0.009	0.021	0.681	0.004 49	958.5
	rs1576901	9	A	T	0.714	0.096	0.020	1.47 × 10^-6	0.032	0.017	0.064	0.003 80	811.1
	rs2864700	1	C	T	0.762	0.144	0.028	2.23 × 10^-7	-0.044	0.023	0.050	0.007 55	1 615.3
	rs4635671	3	G	T	0.213	-0.103	0.022	3.41 × 10^-6	0.031	0.019	0.103	0.003 54	755.2
	rs73573476	19	G	A	0.739	0.238	0.050	1.91 × 10^-6	0.011	0.041	0.795	0.021 77	4 728.3
	rs77430782	19	C	T	0.729	0.101	0.022	4.86 × 10^-6	-0.019	0.019	0.318	0.004 01	855.6
	rs948367	11	C	T	0.175	-0.087	0.019	4.14 × 10^-6	0.008	0.016	0.629	0.002 19	465.9
	合计^a											0.006 40	1 376.0

人群	结局	暴露因素	方法	OR	95% CI	P值
欧洲	牙周炎	骨密度^a	IVW	0.964	0.902 ~ 1.030	0.281
			WM	0.986	0.886 ~ 1.097	0.797
			MR-Egger	0.896	0.781 ~ 1.027	0.117
东亚	牙周病	骨质疏松症	IVW	0.892	0.782 ~ 1.018	0.090
			WM	0.916	0.760 ~ 1.104	0.387
			MR-Egger	1.110	0.656 ~ 1.842	0.734

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