Table S2. Selection of valid genetic instruments based on UKB and Wittemans’s study.

UKB
SNP	Chr	Pos	EA	NEA	EAF	β	Se	P	Loci
Note: “–” means Gene loci was not found. We excluded rs1047891 (homocysteine levels), rs11666281 (body mass index), rs13107325 (diastolic blood pressure), rs1801133 (homocysteine levels), rs2657879 (fasting blood glucose), rs28601761 (triglycerides), rs36105243 (type 2 diabetes), rs4240624 (total cholesterol), rs56113850 (smoking status: current), rs6601302 (body mass index), and rs79687284 (diabetes diagnosed by doctors) for pleiotropic effects (from PhenoScanner). Abbreviation: UKB=UK Biobank; Chr=chromosome; Pos=position; EA=equal alleles; NEA=non-equal alleles; EAF=equal allele frequencies; Se=standard error; SNP=single nucleotide polymorphism; PSPH=phosphoserine phosphatase; GLDC=glycine decarboxylase; GCSH=glycine cleavage system protein H. * means loci related to circulating glycine. †means the SNPs used in this study.
rs10190808* ,†	2	211993631	C	G	0.136421	0.0346173	0.0056719	2.40×10 −9	CPS1-IT1
rs10934753* ,†	3	125906179	A	G	0.417116	0.0690031	0.0039623	3.40×10 −74	ALDH1L1
rs11045886	12	21386493	C	A	0.165117	0.0306817	0.0052791	8.30×10 −9	SLCO1B1
rs11172190	12	57766305	T	C	0.503709	0.0236924	0.0039114	1.00×10 −10	R3HDM2
rs112247225 †	16	81154900	T	C	0.046621	−0.128232	0.0092851	5.20×10 −45	PKD1L2
rs11242109	5	131677047	T	G	0.47905	0.0226052	0.003901	2.00×10 −8	SLC22A4
rs149181595	15	43685807	C	A	0.027601	0.0942587	0.0119122	3.90×10 −17	TUBGCP4
rs17722201	2	209645912	C	T	0.219135	0.0275746	0.0047091	9.80×10 −9	PTH2R
rs192322963 †	8	17445955	A	G	0.025449	0.0829439	0.0125376	4.10×10 −11	PDGFRL
rs1965869 †	4	89677537	C	T	0.715726	−0.0242087	0.0043317	9.00×10 −9	FAM13A
rs2026972* ,†	9	6538279	C	G	0.308331	−0.0821551	0.0042321	2.20×10 −87	GLDC
rs2608913 †	6	131870261	C	T	0.217028	−0.0243496	0.0047367	2.30×10 −8	ARG1
rs2657879 †	12	56865338	G	A	0.182536	0.0478885	0.0050385	5.20×10 −22	GLS2
rs2711697 †	12	47265729	C	A	0.369926	0.0265213	0.0040341	1.10×10 −11	SLC38A4
rs28435239	9	5989087	A	G	0.769224	−0.0289595	0.0046491	8.60×10 −10	KIAA2026
rs34945403 †	15	58430763	G	A	0.067631	−0.0634669	0.0080365	1.70×10 −15	AQP9
rs35034344 †	2	211026796	T	A	0.273031	−0.0653462	0.0045911	1.90×10 −46	KANSL1L
rs4380169	2	212145768	C	T	0.490602	−0.0421118	0.0038951	3.60×10 −27	ENSAP3
rs4889229	16	81113672	T	C	0.917408	0.117726	0.0071008	4.20×10 −64	RP11-303E16.10
rs561931* ,†	1	120254506	G	A	0.580975	0.0290991	0.0039588	4.50×10 −14	PHGDH
rs56819961 †	12	47137673	C	T	0.212573	0.0426129	0.0047614	1.40×10 −20	SLC38A4
rs6587644	1	151994458	A	G	0.304982	0.0221024	0.0042589	2.40×10 −8	NBPF18P
rs67523949	12	348506	T	C	0.536231	0.0263338	0.0039096	3.30×10 −11	SLC6A13
rs7188156	16	79938114	G	T	0.14474	0.0317192	0.0055593	1.20×10 −8	LINC01228
rs75604103 †	2	211692010	G	A	0.121625	−0.0989874	0.0060071	1.10×10 −60	ENSAP3
rs7704653 †	5	90255685	G	A	0.724033	−0.0316456	0.0044087	3.70×10 −13	ADGRV1
rs7800001 †	7	56072010	C	T	0.755284	0.0723549	0.0045524	5.50×10 −61	GBAS
rs79687284 †	1	214150821	C	G	0.034645	0.0679817	0.0106777	7.80×10 −11	PROX1-AS1
rs9532939 †	13	42440496	A	T	0.345473	0.0252027	0.0042637	8.70×10 −9	VWA8
rs11666281	19	18234588	T	C	0.25424	0.0044789	−0.0370833	1.30×10 −17	MAST3
rs6601302 †	8	9239458	G	T	0.750342	0.004516	0.0276846	2.10×10 −10	−
rs2657879 †	12	56865338	G	A	0.182536	0.0050385	0.0478885	5.20×10 −22	GLS2
rs28601761 †	8	126500031	G	C	0.420161	0.003998	0.060914	1.40×10 −55	TRIB1
rs4240624	8	9184231	A	G	0.90923	0.0067925	−0.126861	2.00×10 −82	LOC157273
Wittemans’s study
rs4646961	1	76217169	A	G	0.297	0.048	0.006	8.41×10 −19	intronic variant in ACADM
rs561931* ,†	1	120254506	G	A	0.593	0.033	0.006	7.57×10 −14	5’ UTR variant of PHGDH
rs10184004 †	2	165508389	T	C	0.4	0.036	0.006	1.53×10 −9	Intergenic variant near COBLL1 (28 kb) and GRB14 (30 kb)
rs715* ,†	2	211543055	C	T	0.313	0.444	0.006	3.00×10 −1632	3’UTR variant of CPS1
rs9862438*	3	125910381	T	C	0.416	0.058	0.006	1.13×10 −30	ncRNA intronic variant in ALDH1L1-AS2
rs148685782	4	155533035	G	C	0.996	0.309	0.049	2.01×10 −10	Synonymous variant in FGG
rs71640034	4	187161048	A	G	0.511	0.034	0.006	5.57×10 −8	intronic variant in KLKB1
rs156380	5	53378450	C	T	0.807	0.031	0.007	4.50×10 −8	intronic variant in ARL15
rs3105793	5	90226061	A	G	0.273	0.028	0.006	4.04×10 −8	intronic variant in ADGRV1
rs10900807	5	131757480	G	C	0.805	0.036	0.007	1.26×10 −9	ncRNA intronic variant in C5orf56
rs2545801	5	176841339	C	T	0.747	0.042	0.007	7.23×10 −14	intergenic variant near F12 (5 kb) and GRK6 (12 kb)
rs543159	6	160776017	A	C	0.482	0.035	0.006	4.20×10 −10	intronic variant in SLC22A3
rs4947534*	7	56079094	C	T	0.76	0.072	0.007	7.12×10 −34	3’ UTR variant of PSPH
rs9987289 †	8	9183358	A	G	0.1	0.124	0.01	1.74×10 −49	ncRNA intronic variant in LOC157273
rs28601761 †	8	126500031	G	C	0.416	0.063	0.006	8.49×10 −30	intergenic variant near TRIB1 (49kb) and LINC00861 (435 kb)
rs17591030*	9	6550024	C	T	0.715	0.08	0.006	1.88×10 −40	intron variant in GLDC
rs676996 †	9	136146077	T	G	0.668	0.04	0.006	4.39×10 −15	intron variant in ABO
rs190595610	10	32274880	A	G	0.997	0.253	0.056	8.96×10 −9	Intergenic variant near ARHGAP12 (57 kb) and KIF5B (23 kb)
rs10740134 †	10	65315433	T	C	0.515	0.038	0.006	1.18×10 −12	intron variant in REEP3
rs12297321	12	47109387	T	C	0.152	0.048	0.008	7.41×10 −13	Intergenic variant near SLC38A4 (38 kb) and LOC100288798 (630 kb)
rs2638314	12	56866334	A	T	0.182	0.042	0.007	1.52×10 −8	intronic variant in GLS2
rs9514191	13	104520138	C	G	0.312	0.034	0.006	3.10×10 −8	intergenic variant near LINC01309 (440 kb) and DAOA-AS1(159 kb)
rs201393666	15	43677979	A	C	0.029	0.097	0.017	2.64×10 −8	intronic variant in TUBGCP4
rs2280195	15	58467095	A	G	0.441	0.028	0.006	3.15×10 −9	intronic variant in AQP9
rs9923732*	16	81110903	A	G	0.914	0.119	0.011	1.22×10 −41	Upstream variant of C16orf46, 9 kb downstream of GCSH
rs8078686 †	17	45735706	C	T	0.509	0.035	0.006	3.66×10 −11	intron variant in KPNB1
rs273510 †	19	18223350	A	G	0.708	0.034	0.006	3.57×10 −9	intron variant in MAST3