Bidirectional Mendelian randomization study of causality between body mass index and type 2 diabetes in a European population

doi:10.3969/j.issn.1004-583X.2024.04.005

Abstract

Abstract:

Objective The causal association between body mass index (BMI) and type 2 diabetes mellitus (T2DM) was evaluated by bidirectional Mendelian randomization (MR). Methods Statistical data were pooled using the publicly available Genome-wide association study (GWAS). A total of 461460 cases of BMI and 655666 cases of T2DM were obtained. Totally 373 Single Nucleotide Polymorphisms (SNPs) genetic variations closely related to T2DM were selected as forward instrumental variables, and 118 SNPs were selected as reverse instrumental variables. Inverse variance weighted (IVW), Weighted median (WME), MR-Egger, Simple mode, and weighted mode were used for two-way MR analysis, and odds ratio (OR) values were used to evaluate the causal relationship between BMI and T2DM. The heterogeneity test, pleiotropy test, and leave-one-out method were further used for sensitivity analysis to evaluate the robustness and reliability of the results. Results IVW showed a significant positive correlation between BMI and the incidence of T2DM, OR was 2.88, 95% confidence interval (CI) was 2.66-3.12, P value was 5.37e-87. Other methods showed similar cause-and-effect relationships. In addition, horizontal pleiotropy was not observed by the horizontal pleiotropy test (P=0.25). Reverse MR analysis did not observe reverse causality between BMI and T2DM. Conclusion There may be a positive causal relationship between BMI and T2DM.

Key words: type 2 diabetes mellitus, Mendelian randomization, body mass index, causal relationship

CLC Number:

R587.1

Sun Hui, Liu Haiying, Ren Junhao, Li Jinxia. Bidirectional Mendelian randomization study of causality between body mass index and type 2 diabetes in a European population[J]. Clinical Focus, 2024, 39(4): 325-331.

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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2024.04.005

https://huicui.hebmu.edu.cn/EN/Y2024/V39/I4/325

Figures/Tables 9

References 26

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Trait	GWAS ID	Sample size	N (case)	N (control)	Number of SNPs	Population	Sex	Year
BMI	ukb-b-19953	461, 460	N/A	N/A	9, 851, 867	European	Males and Females	2018
T2DM	ebi-a-GCST006867	655, 666	61714	1178	5, 030, 727	European	Males and Females	2018

Trait	GWAS ID	Sample size	N (case)	N (control)	Number of SNPs	Population	Sex	Year
BMI	ukb-b-19953	461, 460	N/A	N/A	9, 851, 867	European	Males and Females	2018
T2DM	ebi-a-GCST006867	655, 666	61714	1178	5, 030, 727	European	Males and Females	2018

Number	SNPs	Pos	CHR	EAF	EA	OA	Beta	SE	P	F
1	rs1000096	38692835	4	0.39594	T	C	-0.0133384	0.002031	5.10E-11	43.13038659
2	rs10063055	140990108	5	0.251841	T	C	0.0136775	0.00227	1.70E-09	36.30748534
3	rs10099330	143383694	8	0.449841	G	A	0.0124247	0.001989	4.20E-10	39.01860049
4	rs10160769	76474827	11	0.214929	C	G	-0.0155862	0.002422	1.20E-10	41.41291473
5	rs10169594	41637688	2	0.360259	C	T	0.0121875	0.002055	3.00E-09	35.17063788
6	rs10172070	208307761	2	0.144835	T	C	0.0161392	0.002784	6.70E-09	33.61826643
7	rs10182416	104242992	2	0.511854	G	A	0.0130378	0.001971	3.70E-11	43.74068309
8	rs10505836	19288508	12	0.860918	C	A	0.0184851	0.002871	1.20E-10	41.45907232
9	rs1064213	118650996	10	0.246269	T	C	0.0175643	0.002298	2.20E-14	58.37631077
10	rs10742752	198950240	2	0.480617	A	G	0.0149301	0.001971	3.70E-14	57.32304216

Number	SNPs	Pos	CHR	EAF	EA	OA	Beta	SE	P	F
1	rs1000096	38692835	4	0.39594	T	C	-0.0133384	0.002031	5.10E-11	43.13038659
2	rs10063055	140990108	5	0.251841	T	C	0.0136775	0.00227	1.70E-09	36.30748534
3	rs10099330	143383694	8	0.449841	G	A	0.0124247	0.001989	4.20E-10	39.01860049
4	rs10160769	76474827	11	0.214929	C	G	-0.0155862	0.002422	1.20E-10	41.41291473
5	rs10169594	41637688	2	0.360259	C	T	0.0121875	0.002055	3.00E-09	35.17063788
6	rs10172070	208307761	2	0.144835	T	C	0.0161392	0.002784	6.70E-09	33.61826643
7	rs10182416	104242992	2	0.511854	G	A	0.0130378	0.001971	3.70E-11	43.74068309
8	rs10505836	19288508	12	0.860918	C	A	0.0184851	0.002871	1.20E-10	41.45907232
9	rs1064213	118650996	10	0.246269	T	C	0.0175643	0.002298	2.20E-14	58.37631077
10	rs10742752	198950240	2	0.480617	A	G	0.0149301	0.001971	3.70E-14	57.32304216

Number	SNPs	Position	CHR	EAF	EA	OA	β	SE	P	F
1	rs10077431	112927686	5	0.21786	A	C	-0.0487	0.0089	4.75E-08	29.94180028
2	rs10087241	30863722	8	0.593614	A	G	-0.0475	0.008	2.80E-09	35.25390625
3	rs10100265	10633159	8	0.613716	C	A	-0.0491	0.0079	6.29E-10	38.62858516
4	rs10114341	96919182	9	0.44029	C	T	-0.0409	0.0072	1.15E-08	32.26871142
5	rs10401969	19407718	19	0.076171	C	T	0.0921	0.0133	4.13E-12	47.95302165
6	rs1050226	7281654	6	0.408461	G	A	-0.0491	0.0074	3.34E-11	44.02501826
7	rs1061813	14847331	5	0.535045	A	G	-0.0429	0.0073	3.37E-09	34.5357478
8	rs1063355	32627714	6	0.609122	G	T	0.0709	0.0079	3.72E-19	80.54494472
9	rs10740322	71485458	10	0.6872	A	G	0.0477	0.0085	2.11E-08	31.49190311
10	rs10811661	22134094	9	0.173071	C	T	-0.1569	0.0098	4.13E-58	256.3266347