Does Walking Have an Association with Osteoarthritis? A Two-Sample Mendelian Randomization Analysis

Figures & data

Figure 1 Selecting instrumental variables.

Abbreviations: SNP, Single nucleotide polymorphism; BMI, Body Mass Index; OA, Osteoarthritis; KOA, Knee osteoarthritis; HOA, Hip osteoarthritis; IVW, Inverse variance weighting.

Table 1 SNPs Strongly Associated with Exposure

SNP	Effect Allele	Other Allele	Beta	SE	P value	F
rs6739738	T	C	−0.00562931	0.000936803	1.90E-09	36.10886065
rs11896330	A	G	−0.00594477	0.000976222	1.10E-09	37.08283528
rs7610856	A	C	0.00559921	0.000949233	3.70E-09	34.79428018
rs7617548	C	T	−0.00642781	0.00115066	2.30E-08	31.20556352
rs2910829	A	G	0.00546852	0.0009513	9.00E-09	33.04491325
rs2670012	T	C	0.00582567	0.000946359	7.50E-10	37.89482682
rs1927902	C	T	0.0061759	0.00107623	9.60E-09	32.92989325
rs3026380	C	G	0.00571482	0.00100974	1.50E-08	32.03214268
rs1827089	A	G	−0.00634604	0.00113219	2.10E-08	31.41716414
rs61955196	C	G	−0.00609887	0.00103066	3.30E-09	35.01611096
rs7133277	A	G	0.00541499	0.000980372	3.30E-08	30.50798469
rs7207400	C	T	0.00585611	0.00105208	2.60E-08	30.98281845
rs34224566	T	C	−0.00616836	0.00105771	5.50E-09	34.00996647
rs968807	G	A	−0.0052677	0.000940533	2.10E-08	31.36851728
rs613872	T	G	−0.00746357	0.00123488	1.50E-09	36.52949825
rs1941943	T	C	0.00631248	0.00113847	2.90E-08	30.7437506

Abbreviations: SNP, Single Nucleotide Polymorphism; SE, standard error; F, F-statistic.

Table 2 MR Result

Outcomes	MR Result	OR	L-95% CI	U-95% CI	P value
Osteoarthritis (Knee or Hip) SNP=16	MR Egger	0.1183	6.11E-07	22,914.0401	0.7362
	Weighted median	0.4397	0.1601	1.2074	0.1109
	IVW	0.3224	0.1261	0.8243	0.0181
	Simple mode	0.5672	0.1	3.2335	0.5328
	Weighted mode	0.5673	0.1177	2.7349	0.4908
Knee osteoarthritis SNP=16	MR Egger	0.0152	1.64E-08	14,124.8144	0.56
	Weighted median	0.2672	0.0803	0.8892	0.0314
	IVW	0.1396	0.0484	0.4026	0.0003
	Simple mode	0.292	0.0383	2.2262	0.2534
	Weighted mode	0.3186	0.0484	2.0958	0.2525
Osteoarthritis (hip) SNP=16	MR Egger	30.6011	1.94E-09	4.83E+11	0.7794
	Weighted median	0.7314	0.1656	3.2304	0.6798
	IVW	1.2075	0.1978	7.3727	0.8381
	Simple mode	1.3176	0.1211	14.3407	0.8239
	Weighted mode	1.2596	0.1401	11.324	0.8396

Abbreviations: IVW, Inverse variance weighting; OR, Odds Ratio; L-95% CI, Lower 95% confidence interval; U-95% CI, Upper 95% confidence interval; SNP, Single nucleotide polymorphism; MR, Mendelian randomization.

Table 3 Sensitivity Analysis and Pleiotropy Test

Outcome		OA	KOA	HOA
IVW (heterogeneity)	p value	0.0216	0.0672	0.0001
	Q	27.9905	23.8771	44.1875
MR Egger (heterogeneity)	p value	0.0145	0.0497	0.0001
	Q	27.9382	23.7068	43.9575
MR Egger (pleiotropy)	p value	0.8737	0.7558	0.7906
	Intercept	0.006	0.0132	−0.0192

Abbreviations: OA, Osteoarthritis; KOA, Knee osteoarthritis; HOA, Hip osteoarthritis; MR, Mendelian randomization; IVW, Inverse variance weighting.

Figure 2 Mendelian randomization forest plot, after removing heterogeneity, depicting the impact of walking on OA.

Abbreviations: OR, odds ratio; pval, p-value.