Effects of thyroid-stimulating hormone and sensitivity to thyroid hormones on the risk of hyperuricemia in euthyroid adults

Ding, Hongzhan; Liang, Yanyu; Wang, Yilin; Zhang, Kexin; Zhu, Mengya; Jing, Yang; Xue, Yong; Chen, Xiaofang; Zhou, Hui; Dong, Chen

doi:10.20945/2359-4292-2024-0378

person Hongzhan Ding

contributed to critical revisions of the manuscript · contributed to the acquisition of data · contributed to the statistics analysis · contributed to manuscript drafting · read · approved the final manuscript

schoolDepartment of Epidemiology and Statistics, School of Public Health, Medical College of Soochow University, Soochow, China # These authors contributed equally to this work

0009-0001-9456-5293

person Yanyu Liang

contributed to the acquisition of data · contributed to the statistics analysis · contributed to manuscript drafting · read · approved the final manuscript

schoolDepartment of Epidemiology and Statistics, School of Public Health, Medical College of Soochow University, Soochow, China # These authors contributed equally to this work

0009-0006-8642-0517

person Yilin Wang

contributed to the acquisition of data · contributed to the statistics analysis · contributed to manuscript drafting · read · approved the final manuscript

schoolHuai’an Third Hospital, Huai’an, China # These authors contributed equally to this work

0009-0008-8895-0583

person Kexin Zhang

contributed to the statistics analysis · read · approved the final manuscript

schoolSuzhou Industrial Park Center for Disease Control and Prevention, Soochow, China

0009-0002-7362-3260

person Mengya Zhu

contributed to the acquisition of data · read · approved the final manuscript

schoolHuai’an Third Hospital, Huai’an, China

0009-0008-2900-4909

person Yang Jing

contributed to the statistics analysis · read · approved the final manuscript

schoolSuzhou Industrial Park Center for Disease Control and Prevention, Soochow, China

0009-0009-5482-499X

person Yong Xue

contributed to the statistics analysis · read · approved the final manuscript

schoolHuai’an Third Hospital, Huai’an, China

0009-0007-7860-1526

person Xiaofang Chen

contributed to the acquisition of data · read · approved the final manuscript

schoolSuzhou Industrial Park Center for Disease Control and Prevention, Soochow, China

0009-0005-3062-7124

person Hui Zhou

contributed to critical revisions of the manuscript · contributed to the conception · design of the study · read · approved the final manuscript

schoolSuzhou Industrial Park Center for Disease Control and Prevention, Soochow, China * Hui Zhou and Chen Dong are the joint corresponding authors of this article.

0009-0004-5801-6686

person Chen Dong

contributed to critical revisions of the manuscript · contributed to the conception · design of the study · read · approved the final manuscript · contributed to manuscript drafting

schoolDepartment of Epidemiology and Statistics, School of Public Health, Medical College of Soochow University, Soochow, China * Hui Zhou and Chen Dong are the joint corresponding authors of this article.

0000-0001-5175-1662

Declaration of interest:

there are no conflicts of interest.

personCorrespondence to: Hui Zhou, Suzhou Industrial Park Center for Disease Control and Prevention, Soochow, China,
email4146905@qq.com

Chen Dong, Department of Epidemiology and Statistics, School of Public Health, Medical College of Soochow University, 199 Ren’ai Road, Soochow, Jiangsu, China,
emailcdong@suda.edu.cn

#

These authors contributed equally to this work

Characteristics	TSH (mIU/L)				p-value
Characteristics	Quartile 1	Quartile 2	Quartile 3	Quartile 4	p-value
N	492	494	493	493	-
Age (years)	50 (46, 55)	49 (45, 53)	49 (46, 56)	50 (45, 56)	0.01
Male, n (%)	232 (47.2)	193 (39.1)	168 (34.1)	114 (23.1)	<0.01
Current smoking, n (%)	165 (33.5)	135 (27.3)	107 (21.7)	58 (11.8)	<0.01
Heavy drinking, n (%)	107 (21.7)	89 (18.0)	87 (17.6)	39 (7.9)	<0.01
Hypertension, n (%)	180 (36.6)	170 (34.4)	195 (39.6)	174 (35.3)	0.36
Diabetes, n (%)	51 (10.4)	43 (8.7)	54 (11.0)	40 (8.1)	0.38
Dyslipidemia, n (%)	173 (35.2)	170 (34.4)	163 (33.1)	148 (30.0)	0.34
BMI (kg/m²)	23.50±2.89	23.50±2.75	23.68±2.91	23.53±2.82	0.72
WHR	0.87±0.06	0.88±0.07	0.87±0.06	0.87±0.07	0.07
FT3 (pmol/L)	4.26 (3.94, 4.80)	4.29 (3.95, 4.80)	4.21 (3.90, 4.67)	4.19 (3.86, 4.58)	<0.01
FT4 (pmol/L)	12.85 (11.71, 13.98)	12.67 (11.57, 13.91)	12.48 (11.42, 13.68)	12.45 (11.45, 13.68)	<0.01
TSH (mIU/L)	0.87 (0.72, 0.98)	1.35 (1.23, 1.49)	2.00 (1.79, 2.26)	3.16 (2.87, 3.67)	<0.01
ALT (U/L)	22.07±15.04	21.46±14.79	22.36±17.37	20.41±13.13	0.19
AST (U/L)	23.24±8.79	22.81±8.93	24.17±11.16	23.13±7.20	0.11
TC (mmol/L)	4.79 (4.25, 5.34)	4.77 (4.21, 5.43)	4.79 (4.28, 5.37)	4.84 (4.25, 5.36)	0.88
TG (mmol/L)	1.06 (0.79, 1.48)	1.19 (0.82, 1.55)	1.21 (0.83, 1.63)	1.22 (0.86, 1.63)	0.03
LDL-C (mmol/L)	2.98 (2.55, 3.47)	2.98 (2.55, 3.52)	2.98 (2.55, 3.44)	2.98 (2.47, 3.43)	0.63
HDL-C (mmol/L)	1.18 (1.01, 1.35)	1.15 (1.00, 1.40)	1.18 (1.04, 1.38)	1.22 (1.07, 1.39)	0.02
eGFR(mL/min/1.73 m²)	103.8±9.49	104.95±8.93	103.78±8.57	103.97±9.62	0.14
SUA (μmol/L)	303 (245, 343)	296 (253, 342)	303 (264, 339)	292 (251, 333)	0.12
TFQI	-0.34±0.30	-0.12±0.30	0.11±0.31	0.35±0.29	<0.01
TT4RI	10.74 (8.96, 12.89)	16.98 (15.11, 19.41)	25.01 (21.70, 29.17)	39.87 (34.95, 46.51)	<0.01
TSHI	1.55±0.35	2.01±0.26	2.40±0.28	2.87±0.27	<0.01
FT3/FT4 ratio	0.34±0.06	0.35±0.06	0.35±0.06	0.34±0.05	0.48

	Model 1		Model 2		Model 3
	HR (95% CI)	p-value	HR (95% CI)	p-value	HR (95% CI)	p-value
TSH, mIU/L
Q1 (<1.10)	ref.		ref.		ref.
Q2 (≥1.10, and <1.63)	1.18 (0.79, 1.75)	0.42	1.26 (0.85, 1.88)	0.25	1.26 (0.85, 1.88)	0.26
Q3 (≥1.63, and <2.52)	1.64 (1.13, 2.37)	0.01	1.74 (1.20, 2.52)	<0.01	1.62 (1.11, 2.36)	0.01
Q4 (≥2.52)	1.68 (1.16, 2.43)	<0.01	1.86 (1.28, 2.71)	<0.01	1.87 (1.28, 2.73)	<0.01
P for trend		<0.01		<0.01		<0.01
per 1 SD	1.25 (1.11, 1.41)	<0.01	1.30 (1.15, 1.46)	<0.01	1.29 (1.14, 1.46)	<0.01
TFQI
G1 (≥-1, and < -0.28)	ref.		ref.		ref.
G2 (≥-0.28, and <0)	1.31 (0.89, 1.92)	0.17	1.31 (0.89, 1.92)	0.17	1.36 (0.93, 2.00)	0.12
G3 (≥0, and <0.28)	1.33 (0.90, 1.96)	0.15	1.37 (0.92, 2.02)	0.12	1.24 (0.83, 1.84)	0.29
G4 (≥0.28, and ≤1)	2.02 (1.41, 2.89)	<0.01	2.06 (1.44, 2.96)	<0.01	1.92 (1.33, 2.76)	<0.01
P for trend		<0.01		<0.01		<0.01
per 1 SD	1.31 (1.16, 1.49)	<0.01	1.33 (1.17, 1.51)	<0.01	1.31 (1.16, 1.49)	<0.01
TT4RI
Q1 (<13.79)	ref.		ref.		ref.
Q2 (≥13.79, and <20.51)	1.05 (0.70, 1.59)	0.81	1.08 (0.72, 1.63)	0.71	1.05 (0.69, 1.58)	0.83
Q3 (≥20.51, and <31.74)	1.64 (1.13, 2.38)	<0.01	1.76 (1.21, 2.55)	<0.01	1.67 (1.15, 2.43)	<0.01
Q4 (≥31.74)	1.89 (1.32, 2.72)	<0.01	2.04 (1.41, 2.94)	<0.01	1.93 (1.34, 2.80)	<0.01
P for trend		<0.01		<0.01		<0.01
per 1 SD	1.31 (1.16, 1.47)	<0.01	1.34 (1.19, 1.51)	<0.01	1.32 (1.17, 1.49)	<0.01
TSHI
Q1 (<1.79)	ref.		ref.		ref.
Q2 (≥1.79, and <2.21)	1.25 (0.83, 1.87)	0.29	1.27 (0.84, 1.90)	0.26	1.27 (0.84, 1.90)	0.26
Q3 (≥2.21, and <2.64)	1.79 (1.23, 2.62)	<0.01	1.88 (1.29, 2.75)	<0.01	1.81 (1.23, 2.66)	<0.01
Q4 (≥2.64)	2.01 (1.39, 2.92)	<0.01	2.14 (1.47, 3.11)	<0.01	2.02 (1.38, 2.95)	<0.01
P for trend		<0.01		<0.01		<0.01
per 1 SD	1.34 (1.18, 1.53)	<0.01	1.37 (1.21, 1.56)	<0.01	1.34 (1.18, 1.53)	<0.01
FT3/FT4 ratio
Q1 (<0.30)	ref.		ref.		ref.
Q2 (≥0.30, and <0.34)	0.90 (0.64, 1.28)	0.56	0.90 (0.64, 1.28)	0.57	0.91 (0.64, 1.29)	0.58
Q3 (≥0.34, and <0.38)	0.72 (0.50, 1.05)	0.09	0.71 (0.49, 1.03)	0.07	0.75 (0.52, 1.09)	0.13
Q4 (≥0.38)	0.84 (0.59, 1.19)	0.32	0.80 (0.56, 1.13)	0.20	0.84 (0.59, 1.19)	0.33
P for trend		0.19		0.11		0.21
per 1 SD	0.95 (0.83, 1.08)	0.42	0.92 (0.81, 1.05)	0.24	0.93 (0.82, 1.07)	0.30

Outcome	No. SNPs	Methods	β or OR (95% CI)	p-value	Q	p-value for heterogeneity	Egger intercept	p-value for pleiotropy
SUA	130	IVW (random-effect)	0.037 (0.017, 0.057)	<0.01	624.39	<0.01	0.00077	0.56
		Weighted median	0.009 (-0.008, 0.025)	0.32	-	-
		MR Egger	0.029 (-0.007, 0.064)	0.12	622.73	<0.01
		Maximum likelihood	0.038 (0.029, 0.047)	<0.01	-	-
		MR RAPS	0.019 (0.002, 0.035)	0.03	-	-
		MR-PRESSO	0.016 (0.001, 0.030)	0.03	-	-
gout	130	IVW (random-effect)	1.0018 (1.0004, 1.0032)	0.01	185.68	<0.01	0.00006	0.44
		Weighted median	1.0018 (0.9988, 1.0029)	0.42	-	-
		MR Egger	1.0008 (0.9984, 1.0035)	0.47	184.82	<0.01
		Maximum likelihood	1.0018 (1.0006, 1.0030)	<0.01	-	-
		MR RAPS	1.0018 (1.0005, 1.0032)	<0.01	-	-
		MR-PRESSO	0.0017 (0.0003, 0.0031)	0.02	-	-

Phenotype	PMID	GWAS ID on OpenGwas website	Consortium or Cohorts	Sample size	Year	Source
TSH	38291025	NA	the ThyroidOmics consortium	271,040	2024	https://transfer.sysepi.medizin.uni-greifswald.de/thyroidomics/datasets/
SUA	34594039	ebi-a-GCST90018977	UK Biobank	343,836	2021	https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST90018977/
Gout	33959723	ebi-a-GCST90038687	UK Biobank	484,598	2021	https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST90038687/

Exposure	SNP	Effect allele	Other allele	EAF	β	SE	p-value	F statistics
TSH	rs10186921	T	C	0.556	0.0381	0.0029	1.05×10^-38	172.60
TSH	rs10254690	T	C	0.5554	0.0168	0.0029	8.05×10^-09	33.56
TSH	rs10263288	A	G	0.8919	-0.032	0.0046	5.37×10^-12	48.39
TSH	rs1033701	A	G	0.2729	-0.1168	0.0032	1.00×10^-200	1332.24
TSH	rs1042673	A	G	0.5406	-0.043	0.0029	9.41×10^-50	219.86
TSH	rs1044474	A	G	0.5499	0.0256	0.0029	9.71×10^-19	77.93
TSH	rs10743983	A	G	0.5451	-0.018	0.0029	7.23×10^-10	38.53
TSH	rs10748781	A	C	0.5743	-0.059	0.003	1.97×10^-87	386.77
TSH	rs10751136	A	G	0.5022	0.0191	0.0029	3.89×10^-11	43.38
TSH	rs10758530	A	G	0.0547	0.0513	0.0069	1.34×10^-13	55.28
TSH	rs10799824	A	G	0.1561	-0.1187	0.004	5.12×10^-194	880.60
TSH	rs10814881	A	C	0.4427	-0.0288	0.0029	2.17×10^-23	98.62
TSH	rs10814915	T	C	0.4385	0.0516	0.0029	8.80×10^-70	316.59
TSH	rs10849108	A	G	0.1772	-0.0279	0.0038	4.25×10^-13	53.91
TSH	rs10878984	T	C	0.3497	-0.0213	0.003	2.08×10^-12	50.41
TSH	rs1114707	T	C	0.3372	0.0207	0.0031	3.03×10^-11	44.59
TSH	rs11190335	A	G	0.4156	0.0166	0.003	2.79×10^-08	30.62
TSH	rs11221835	T	C	0.2335	-0.0221	0.0034	1.33×10^-10	42.25
TSH	rs113360717	T	C	0.0341	0.0814	0.0081	1.38×10^-23	100.99
TSH	rs113599227	T	C	0.0444	-0.0837	0.0074	9.31×10^-30	127.93
TSH	rs114322847	T	C	0.025	-0.1608	0.0097	2.84×10^-61	274.81
TSH	rs115044883	A	G	0.0773	-0.0331	0.0058	1.19×10^-08	32.57
TSH	rs115236194	A	G	0.9782	-0.0662	0.0117	1.48×10^-08	32.01
TSH	rs11672947	T	C	0.392	-0.0236	0.0031	1.36×10^-14	57.96
TSH	rs11675342	T	C	0.4191	0.0281	0.0029	1.34×10^-21	93.89
TSH	rs116909374	T	C	0.0362	-0.1589	0.0085	1.11×10^-78	349.47
TSH	rs117096139	T	C	0.0342	-0.0474	0.0084	1.47×10^-08	31.84
TSH	rs11732564	A	G	0.2797	-0.0254	0.0033	6.50×10^-15	59.24
TSH	rs11830037	A	C	0.0765	0.04	0.0055	3.42×10^-13	52.89
TSH	rs12036629	A	G	0.5306	-0.0317	0.0029	1.25×10^-27	119.49
TSH	rs1203930	A	G	0.2193	-0.0652	0.0035	1.08×10^-78	347.02
TSH	rs12436555	A	G	0.163	-0.0216	0.0039	3.54×10^-08	30.67
TSH	rs12479260	T	C	0.0863	-0.0385	0.0052	1.04×10^-13	54.82
TSH	rs12567744	A	G	0.6838	0.036	0.0031	1.15×10^-30	134.86
TSH	rs1288492	T	C	0.464	0.0185	0.0029	2.94×10^-10	40.70
TSH	rs12889167	T	C	0.5545	0.039	0.0029	1.20×10^-40	180.85
TSH	rs12892248	A	G	0.1249	0.0254	0.0044	7.48×10^-09	33.32
TSH	rs12893275	T	C	0.0904	-0.0392	0.0051	1.32×10^-14	59.08
TSH	rs13138273	A	G	0.7994	0.1107	0.0037	1.00×10^-200	895.14
TSH	rs13286806	A	G	0.4163	-0.0181	0.003	1.42×10^-09	36.40
TSH	rs1342454	A	G	0.0341	0.0548	0.0083	4.36×10^-11	43.59
TSH	rs1385737	T	C	0.1254	-0.036	0.0047	2.47×10^-14	58.67
TSH	rs139242164	T	G	0.0106	0.1158	0.0158	2.55×10^-13	53.72
TSH	rs1458819	T	C	0.8904	0.0276	0.0048	6.34×10^-09	33.06
TSH	rs149363012	T	C	0.0211	0.1247	0.0117	1.90×10^-26	113.59
TSH	rs1496627	A	C	0.5794	0.0212	0.0029	5.31×10^-13	53.44
TSH	rs1690789	T	C	0.4765	-0.0288	0.0029	5.11×10^-23	98.62
TSH	rs17462267	A	C	0.7288	-0.0365	0.0033	6.08×10^-29	122.34
TSH	rs17477923	T	C	0.7483	0.0609	0.0033	7.59×10^-75	340.57
TSH	rs17481499	T	C	0.1696	0.0459	0.0038	9.13×10^-33	145.90
TSH	rs1755770	T	C	0.6013	-0.0246	0.003	1.73×10^-16	67.24
TSH	rs17729624	A	G	0.0998	0.0341	0.0048	1.72×10^-12	50.47
TSH	rs179785	A	G	0.4835	0.0182	0.0029	4.35×10^-10	39.39
TSH	rs1875057	A	G	0.3731	0.0172	0.003	8.74×10^-09	32.87
TSH	rs1883806	T	G	0.3918	0.0198	0.0032	5.21×10^-10	38.28
TSH	rs1969151	T	C	0.2131	0.0202	0.0035	1.24×10^-08	33.31
TSH	rs2031365	T	C	0.2809	0.0486	0.0032	5.37×10^-52	230.66
TSH	rs2229738	T	C	0.0946	-0.0394	0.0055	8.41×10^-13	51.32
TSH	rs2282026	A	G	0.5295	-0.0166	0.0029	8.05×10^-09	32.77
TSH	rs2288188	T	G	0.962	0.0719	0.0079	6.16×10^-20	82.83
TSH	rs2295727	A	G	0.934	-0.0332	0.0059	1.51×10^-08	31.66
TSH	rs2364727	T	C	0.1141	0.0265	0.0047	1.30×10^-08	31.79
TSH	rs2581928	A	G	0.2653	-0.0222	0.0033	8.69×10^-12	45.26
TSH	rs2928167	A	G	0.8648	0.133	0.0043	1.00×10^-200	956.67
TSH	rs3008019	T	G	0.2482	-0.0309	0.0033	2.53×10^-20	87.68
TSH	rs30233	A	G	0.5663	-0.0321	0.003	1.53×10^-27	114.49
TSH	rs3101866	A	G	0.4778	-0.0336	0.0029	2.24×10^-31	134.24
TSH	rs3134107	A	G	0.1786	-0.0231	0.0038	1.11×10^-09	36.95
TSH	rs334699	A	G	0.056	-0.1447	0.0069	6.89×10^-98	439.78
TSH	rs35324752	T	G	0.3598	-0.0198	0.0031	1.29×10^-10	40.79
TSH	rs36259	A	G	0.7565	-0.0247	0.0035	1.86×10^-12	49.80
TSH	rs3808798	T	G	0.2935	-0.0194	0.0032	8.36×10^-10	36.75
TSH	rs4074131	A	G	0.8207	-0.0365	0.004	3.74×10^-20	83.26
TSH	rs41272256	A	C	0.9213	0.0588	0.0054	8.58×10^-28	118.57
TSH	rs4318967	T	C	0.5936	0.0191	0.0031	3.84×10^-10	37.96
TSH	rs4340549	T	C	0.7634	-0.0233	0.0035	1.45×10^-11	44.32
TSH	rs4471862	A	G	0.3238	-0.0248	0.0031	2.40×10^-15	64.00
TSH	rs4608435	T	G	0.2627	-0.0231	0.0033	3.63×10^-12	49.00
TSH	rs4793439	T	C	0.4692	0.0407	0.0029	3.57×10^-45	196.97
TSH	rs4844563	A	C	0.6657	-0.0169	0.0031	3.54×10^-08	29.72
TSH	rs4885687	T	G	0.7344	0.0258	0.0033	5.96×10^-15	61.12
TSH	rs4933466	A	G	0.6025	0.033	0.003	2.67×10^-28	121.00
TSH	rs4934383	T	C	0.6616	-0.0228	0.0031	8.64×10^-14	54.09
TSH	rs523587	T	C	0.4296	0.0163	0.0029	2.29×10^-08	31.59
TSH	rs554833	T	C	0.3491	0.0418	0.003	8.54×10^-44	194.14
TSH	rs55717031	T	G	0.3057	-0.0199	0.0032	4.94×10^-10	38.67
TSH	rs55837101	T	C	0.2249	0.0199	0.0035	1.75×10^-08	32.33
TSH	rs56279106	A	G	0.2726	-0.0195	0.0032	2.03×10^-09	37.13
TSH	rs6133344	T	C	0.5121	-0.024	0.0029	1.43×10^-16	68.49
TSH	rs61938844	A	G	0.0284	0.1721	0.0097	5.52×10^-71	314.79
TSH	rs62192963	A	G	0.1487	0.0324	0.0042	6.44×10^-15	59.51
TSH	rs62506639	T	C	0.8097	-0.0271	0.0037	1.47×10^-13	53.65
TSH	rs6414089	A	G	0.3578	0.0175	0.003	6.44×10^-09	34.03
TSH	rs6494466	A	G	0.263	-0.0198	0.0033	2.08×10^-09	36.00
TSH	rs6546566	T	C	0.6852	0.0182	0.0031	6.65×10^-09	34.47
TSH	rs6567094	A	G	0.5543	0.0309	0.0029	2.22×10^-26	113.53
TSH	rs6805350	T	G	0.9414	-0.0347	0.0062	2.95×10^-08	31.32
TSH	rs700750	A	C	0.6244	0.0308	0.003	3.15×10^-25	105.40
TSH	rs706024	A	G	0.6129	-0.0198	0.003	3.16×10^-11	43.56
TSH	rs7211380	A	G	0.9292	0.0472	0.0056	5.20×10^-17	71.04
TSH	rs7248104	A	G	0.4062	-0.0584	0.003	3.20×10^-87	378.95
TSH	rs72682433	T	C	0.8965	-0.035	0.0048	2.32×10^-13	53.17
TSH	rs7315310	A	G	0.4034	-0.0203	0.003	1.25×10^-11	45.79
TSH	rs73226434	T	C	0.1738	-0.039	0.0038	1.23×10^-24	105.33
TSH	rs73575083	A	G	0.6747	0.0923	0.0031	3.03×10^-199	886.50
TSH	rs737308	T	G	0.2759	-0.0925	0.0033	1.02×10^-177	785.69
TSH	rs751171	T	C	0.6647	-0.0358	0.0031	9.06×10^-31	133.36
TSH	rs7529705	A	G	0.3744	0.053	0.003	9.08×10^-71	312.11
TSH	rs7589228	A	C	0.6294	0.0264	0.003	2.43×10^-18	77.44
TSH	rs76697438	A	G	0.0129	-0.1041	0.0151	4.75×10^-12	47.53
TSH	rs768356	T	C	0.7996	-0.0741	0.0036	1.35×10^-92	423.67
TSH	rs78218421	T	C	0.0627	0.044	0.0062	9.05×10^-13	50.36
TSH	rs78404781	A	G	0.9865	0.1834	0.0155	2.86×10^-32	140.00
TSH	rs78856554	A	G	0.0916	0.0377	0.0051	9.04×10^-14	54.64
TSH	rs79259951	A	C	0.9314	0.0367	0.0057	1.39×10^-10	41.46
TSH	rs79496463	T	C	0.043	0.046	0.0078	3.01×10^-09	34.78
TSH	rs7955258	A	G	0.4162	-0.0473	0.003	1.97×10^-54	248.59
TSH	rs80220524	T	C	0.0243	0.0619	0.0102	1.17×10^-09	36.83
TSH	rs879736	T	C	0.1678	0.0259	0.0039	4.24×10^-11	44.10
TSH	rs925489	T	C	0.6528	0.0749	0.003	4.50×10^-138	623.33
TSH	rs9298749	A	C	0.6132	-0.0317	0.003	3.50×10^-26	111.65
TSH	rs9365939	A	G	0.4561	-0.0195	0.0029	1.99×10^-11	45.21
TSH	rs9396865	T	C	0.8409	-0.0297	0.0039	4.57×10^-14	57.99
TSH	rs9497965	T	C	0.3956	0.0328	0.0029	9.03×10^-29	127.92
TSH	rs9521826	A	G	0.7318	0.025	0.0033	1.88×10^-14	57.39
TSH	rs9537312	T	C	0.2063	-0.0235	0.0036	4.37×10^-11	42.61
TSH	rs9729157	T	C	0.6356	0.0222	0.003	1.76×10^-13	54.76
TSH	rs9772642	T	C	0.7023	-0.0285	0.0032	1.84×10^-19	79.32
TSH	rs9889941	A	C	0.7036	0.0184	0.0032	7.30×10^-09	33.06
TSH	rs9928281	A	G	0.8914	-0.0344	0.005	7.94×10^-12	47.33

	eGFR		SUA
	β (95% CI)	p-value	β (95% CI)	p-value
TSH	-0.539 (-0.933, -0.145)	0.01	4.236 (1.804, 6.668)	<0.01
TFQI	-1.243 (-2.203, -0.283)	<0.01	6.711 (0.788, 12.633)	0.03
TT4RI	-0.045 (-0.075, -0.015)	<0.01	0.341 (0.154, 0.527)	<0.01
TSHI	-1.008 (-1.675, -0.341)	<0.01	7.593 (3.492, 11.694)	<0.01
FT3/FT4 ratio	1.480 (-5.113, 8.072)	0.66	-75.62 (-115.14, -36.10)	<0.01

TSHI	Model 1		Model 2		Model 3
TSHI	HR (95% CI)	p-value	HR (95% CI)	p-value	HR (95% CI)	p-value
Consider eGFR as time dependent covariatea
Q1 (<1.79)	ref.		ref.		ref.
Q2 (≥1.79, and <2.21)	1.25 (0.83, 1.87)	0.29	1.27 (0.84, 1.90)	0.26	1.22 (0.81, 1.83)	0.34
Q3 (≥2.21, and <2.64)	1.79 (1.23, 2.62)	<0.01	1.88 (1.29, 2.75)	<0.01	1.72 (1.17, 2.52)	<0.01
Q4 (≥2.64)	2.01 (1.39, 2.92)	<0.01	2.14 (1.47, 3.11)	<0.01	1.86 (1.27, 2.71)	<0.01
by a new data-set with multiple imputation method for missing data analysis
Q1 (<1.81)	ref.		ref.		ref.
Q2 (≥1.81, and <2.21)	1.13 (0.77, 1.67)	0.53	1.15 (0.78, 1.69)	0.50	1.13 (0.77, 1.67)	0.54
Q3 (≥2.21, and <2.65)	1.62 (1.13, 2.32)	<0.01	1.70 (1.18, 2.44)	<0.01	1.61 (1.12, 2.32)	0.01
Q4 (≥2.65)	1.84 (1.29, 2.62)	<0.01	1.94 (1.36, 2.78)	<0.01	1.82 (1.27, 2.61)	<0.01
Additional adjustment for baseline SUA
Q1 (<1.79)	ref.		ref.		ref.
Q2 (≥1.79, and <2.21)	1.25 (0.83, 1.87)	0.29	1.27 (0.84, 1.90)	0.26	1.25 (0.83, 1.89)	0.29
Q3 (≥2.21, and <2.64)	1.79 (1.23, 2.62)	<0.01	1.88 (1.29, 2.75)	<0.01	1.78 (1.21, 2.63)	<0.01
Q4 (≥2.64)	2.01 (1.39, 2.92)	<0.01	2.14 (1.47, 3.11)	<0.01	2.02 (1.38, 2.95)	<0.01
The adjustment variable BMI was replaced by WHR
Q1 (<1.79)	ref.		ref.		ref.
Q2 (≥1.79, and <2.21)	1.25 (0.83, 1.87)	0.29	1.27 (0.84, 1.90)	0.26	1.28 (0.85, 1.92)	0.24
Q3 (≥2.21, and <2.64)	1.79 (1.23, 2.62)	<0.01	1.88 (1.29, 2.75)	<0.01	1.83 (1.25, 2.68)	<0.01
Q4 (≥2.64)	2.01 (1.39, 2.92)	<0.01	2.14 (1.47, 3.11)	<0.01	2.03 (1.39, 2.96)	<0.01

TFQI	Model 1		Model 2		Model 3
TFQI	HR (95% CI)	p-value	HR (95% CI)	p-value	HR (95% CI)	p-value
Consider eGFR as time dependent covariatea
G1 (≥ -1, and <-0.28)	ref.		ref.		ref.
G2 (≥-0.28, and <0)	1.31 (0.89, 1.92)	0.17	1.31 (0.89, 1.92)	0.17	1.35 (0.92, 1.98)	0.13
G3 (≥0, and <0.28)	1.33 (0.90, 1.96)	0.15	1.37 (0.92, 2.02)	0.12	1.13 (0.77, 1.68)	0.53
G4 (≥0.28, and ≤1)	2.02 (1.41, 2.89)	<0.01	2.06 (1.44, 2.96)	<0.01	1.77 (1.23, 2.55)	<0.01
by a new data-set with multiple imputation method for missing data analysis
G1 (≥ -1, and <-0.28)	ref.		ref.		ref.
G2 (≥-0.28, and <0)	1.38 (0.95, 1.99)	0.09	1.39 (0.96, 2.00)	0.08	1.44 (0.997, 2.09)	0.05
G3 (≥0, and <0.28)	1.26 (0.86, 1.85)	0.23	1.30 (0.89, 1.91)	0.18	1.15 (0.78, 1.70)	0.47
G4 (≥0.28, and ≤1)	1.96 (1.38, 2.78)	<0.01	1.99 (1.40, 2.83)	<0.01	1.86 (1.31, 2.66)	<0.01
Additional adjustment for baseline SUA
G1 (≥ -1, and <-0.28)	ref.		ref.		ref.
G2 (≥-0.28, and <0)	1.31 (0.89, 1.92)	0.17	1.31 (0.89, 1.92)	0.17	1.34 (0.91, 1.98)	0.14
G3 (≥0, and <0.28)	1.33 (0.90, 1.96)	0.15	1.37 (0.92, 2.02)	0.12	1.17 (0.79, 1.75)	0.43
G4 (≥0.28, and ≤1)	2.02 (1.41, 2.89)	<0.01	2.06 (1.44, 2.96)	<0.01	1.91 (1.33, 2.76)	<0.01
The adjustment variable BMI was replaced by WHR
G1 (≥-1, and <-0.28)	ref.		ref.		ref.
G2 (≥-0.28, and <0)	1.31 (0.89, 1.92)	0.17	1.31 (0.89, 1.92)	0.17	1.37 (0.93, 2.01)	0.11
G3 (≥0, and <0.28)	1.33 (0.90, 1.96)	0.15	1.37 (0.92, 2.02)	0.12	1.24 (0.84, 1.84)	0.28
G4 (≥0.28, and ≤1)	2.02 (1.41, 2.89)	<0.01	2.06 (1.44, 2.96)	<0.01	1.90 (1.32, 2.74)	<0.01

TT4RI	Model 1		Model 2		Model 3
TT4RI	HR (95% CI)	p-value	HR (95% CI)	p-value	HR (95% CI)	p-value
Consider eGFR as time dependent covariatea
Q1 (<13.79)	ref.		ref.		ref.
Q2 (≥13.79, and <20.51)	1.05 (0.70, 1.59)	0.81	1.08 (0.72, 1.63)	0.71	1.01 (0.67, 1.52)	0.97
Q3 (≥20.51, and <31.74)	1.64 (1.13, 2.38)	<0.01	1.76 (1.21, 2.55)	<0.01	1.59 (1.09, 2.31)	0.02
Q4 (≥31.74)	1.89 (1.32, 2.72)	<0.01	2.04 (1.41, 2.94)	<0.01	1.82 (1.26, 2.63)	<0.01
by a new data-set with multiple imputation method for missing data analysis
Q1 (<13.93)	ref.		ref.		ref.
Q2 (≥13.93, and <20.59)	1.01 (0.68, 1.50)	0.98	1.03 (0.70, 1.54)	0.87	1.00 (0.67, 1.49)	0.99
Q3 (≥20.59, and <31.89)	1.56 (1.09, 2.24)	0.02	1.66 (1.16, 2.39)	<0.01	1.57 (1.09, 2.26)	0.02
Q4 (≥31.89)	1.83 (1.29, 2.60)	<0.01	1.97 (1.38, 2.80)	<0.01	1.86 (1.30, 2.66)	<0.01
Additional adjustment for baseline SUA
Q1 (<13.79)	ref.		ref.		ref.
Q2 (≥13.79, and <20.51)	1.05 (0.70, 1.59)	0.81	1.08 (0.72, 1.63)	0.71	1.03 (0.68, 1.56)	0.88
Q3 (≥20.51, and <31.74)	1.64 (1.13, 2.38)	<0.01	1.76 (1.21, 2.55)	<0.01	1.62 (1.11, 2.36)	0.01
Q4 (≥31.74)	1.89 (1.32, 2.72)	<0.01	2.04 (1.41, 2.94)	<0.01	1.86 (1.28, 2.70)	<0.01
The adjustment variable BMI was replaced by WHR
Q1 (<13.79)	ref.		ref.		ref.
Q2 (≥13.79, and <20.51)	1.05 (0.70, 1.59)	0.81	1.08 (0.72, 1.63)	0.71	1.04 (0.69, 1.57)	0.84
Q3 (≥20.51, and <31.74)	1.64 (1.13, 2.38)	<0.01	1.76 (1.21, 2.55)	<0.01	1.66 (1.14, 2.41)	<0.01
Q4 (≥31.74)	1.89 (1.32, 2.72)	<0.01	2.04 (1.41, 2.94)	<0.01	1.97 (1.36, 2.85)	<0.01

TSHI	Model 1		Model 2		Model 3
TSHI	HR (95% CI)	p-value	HR (95% CI)	p-value	HR (95% CI)	p-value
Consider eGFR as time dependent covariatea
Q1 (<1.79)	ref.		ref.		ref.
Q2 (≥1.79, and <2.21)	1.25 (0.83, 1.87)	0.29	1.27 (0.84, 1.90)	0.26	1.22 (0.81, 1.83)	0.34
Q3 (≥2.21, and <2.64)	1.79 (1.23, 2.62)	<0.01	1.88 (1.29, 2.75)	<0.01	1.72 (1.17, 2.52)	<0.01
Q4 (≥2.64)	2.01 (1.39, 2.92)	<0.01	2.14 (1.47, 3.11)	<0.01	1.86 (1.27, 2.71)	<0.01
by a new data-set with multiple imputation method for missing data analysis
Q1 (<1.81)	ref.		ref.		ref.
Q2 (≥1.81, and <2.21)	1.13 (0.77, 1.67)	0.53	1.15 (0.78, 1.69)	0.50	1.13 (0.77, 1.67)	0.54
Q3 (≥2.21, and <2.65)	1.62 (1.13, 2.32)	<0.01	1.70 (1.18, 2.44)	<0.01	1.61 (1.12, 2.32)	0.01
Q4 (≥2.65)	1.84 (1.29, 2.62)	<0.01	1.94 (1.36, 2.78)	<0.01	1.82 (1.27, 2.61)	<0.01
Additional adjustment for baseline SUA
Q1 (<1.79)	ref.		ref.		ref.
Q2 (≥1.79, and <2.21)	1.25 (0.83, 1.87)	0.29	1.27 (0.84, 1.90)	0.26	1.25 (0.83, 1.89)	0.29
Q3 (≥2.21, and <2.64)	1.79 (1.23, 2.62)	<0.01	1.88 (1.29, 2.75)	<0.01	1.78 (1.21, 2.63)	<0.01
Q4 (≥2.64)	2.01 (1.39, 2.92)	<0.01	2.14 (1.47, 3.11)	<0.01	2.02 (1.38, 2.95)	<0.01
The adjustment variable BMI was replaced by WHR
Q1 (<1.79)	ref.		ref.		ref.
Q2 (≥1.79, and <2.21)	1.25 (0.83, 1.87)	0.29	1.27 (0.84, 1.90)	0.26	1.28 (0.85, 1.92)	0.24
Q3 (≥2.21, and <2.64)	1.79 (1.23, 2.62)	<0.01	1.88 (1.29, 2.75)	<0.01	1.83 (1.25, 2.68)	<0.01
Q4 (≥2.64)	2.01 (1.39, 2.92)	<0.01	2.14 (1.47, 3.11)	<0.01	2.03 (1.39, 2.96)	<0.01

[1] Model 1: unadjusted.

[2] Model 2: adjusted for age, sex.

[3] Model 3: adjusted for age, sex, BMI(WHR), current smoking, heavy drinking, hypertension, diabetes, dyslipidemia, ALT, AST, baseline eGFR (time dependent covariate).

[TFN1] ^a
Using Time Dependent Covariates in the Cox Model.

[5] Abbreviations: TSHI, thyroid-stimulating hormone index; HR, hazard ratio; CI, confidence interval; eGFR, estimated glomerular filtration rate; HUA, hyperuricemia; BMI, body mass index; WHR, waist-to-hip ratio