Genome-wide association study reveals novel loci for adult type 1 diabetes in a 5-year nested case-control study

Table 1 Characters of participants in the present type 1 diabetes genome-wide association study investigation

	Discovery stage				Validation stage				Combination
	Cases (n = 381)	Controls (n = 377)	P	Cases (n = 404)		Controls (n = 427)	P	Cases (n = 785)		Controls (n = 804)	P
Sex
Male	197	200	0.711a	209		223	0.887a	406		423	0.722a
Female	184	177		195		204		379		381
Age (yr)
mean ± SD	28.45 ± 7.70	28.99 ± 8.01	0.338b	28.53 ± 7.95		28.91 ± 7.67	0.496b	28.49 ± 7.51		28.94 ± 7.98	0.248b
< 25	109	101	0.637a	118		114	0.704a	227		215	0.494a
[25, 35)	180	174		188		203		368		377
≥ 35	92	102		98		110		190		212
BMI (kg/m2)
mean ± SD	21.77 ± 4.10	22.10 ± 4.00	0.266b	21.93 ± 4.26		21.52 ± 3.70	0.146b	21.85 ± 4.18		21.79 ± 3.85	0.773b
< 18.5	60	46	0.371a	51		66	0.500a	111		112	0.985a
[18.5, 25)	270	279		303		311		573		590
≥ 25	51	52		50		50		101		102
Glucose level (mmol/L)
mean ± SD	12.83 ± 2.35	5.43 ± 1.33	< 0.0001b	13.42 ± 2.48		5.53 ± 1.30	< 0.0001b	13.13 ± 2.44		5.49 ± 81.32	< 0.0001b

^aTwo-sided chi-square test.

^bStudents’ t test. BMI: Body mass index.

Table 2 Identification of type 1 diabetes risk loci in a Chinese population

SNPs	Location	Stage	Genotype distribution		ORadd (95%CI)	Pa for Bonferroni
			Cases (n = 785)	Controls (n = 804)
rs55846421	Chr14. 50310401	Discovery	10/149/222	0/6/371	0.024 (0.010-0.056)	4.28 × 10-11
		Validation	8/124/272	2/37/385	0.232 (0.159-0.337)	8.73 × 10-8
		Combination	18/273/494	2/43/756	0.113 (0.081-0.156)	1.76 × 10-9
rs3117017	Chr6. 33095275	Discovery	2/40/339	36/117/224	4.958 (3.107-7.912)	6.36 × 10-5
		Validation	6/32/365	32/98/297	3.202 (2.296-4.466)	4.51 × 10-4
		Combination	8/72/704	68/215/521	3.794 (2.984-4.823)	9.33 × 10-4
rs75836320	Chr12. 65156128	Discovery	8/77/296	1/12/356	0.153 (0.082-0.285)	0.011
		Validation	8/63/333	4/27/396	0.429 (0.289-0.638)	3.3 × 10-4
		Combination	16/140/629	5/39/752	0.283 (0.205-0.392)	1.07 × 10-4
rs362071	Chr22. 20811645	Discovery	82/193/104	46/101/230	0.445 (0.348-0.570)	4.5 × 10-4
		Validation	100/173/131	79/149/199	0.705 (0.588-0.846)	0.0002
		Combination	182/366/235	125/250/429	0.568 (0.495-0.651)	1.66 × 10-4

^aTwo-sided chi-square test. CI: Confidence interval; OR: Odds ratio.

Table 3 The expression and splicing quantitative trait loci analysis of target single nucleotide polymorphisms

SNP name	Influence type	Gene symbol	Expression tissues	P value
rs55846421	eQTLs	ARF6	Cells-cultured fibroblasts	0.00015
		KLHDC1	Brain-cerebellum	0.0000022
			Lung	0.000034
			Thyroid	0.00021
		LRR1	Adipose-subcutaneous	8.00 × 10-10
			Adipose-visceral	5.20 × 10-7
			Breast-mammary tissue	8.70 × 10-7
			Esophagus-muscularis	0.000054
			Lung	0.000077
			Nerve-tibial	0.00013
			Thyroid	0.00016
		RHOQP1	Adipose-subcutaneous	3.30 × 10-8
		RP11-596C23.6	Artery-tibial	1.1 × 10-9
			Esophagus-mucosa	2.3 × 10-9
			Artery-aorta	6.0 × 10-8
			Testis	2.9 × 10-7
			Esophagus-muscularis	0.0000019
			Esophagus-gastroesophageal junction	0.0000025
			Muscle-skeletal	0.0000027
			Small intestine-terminal ileum	0.0000042
			Lung	0.000019
			Colon-sigmoid	0.00002
			Spleen	0.000024
			Artery-coronary	0.000031
			Thyroid	0.000061
			Heart-atrial appendage	0.000062
	sQTLs	RPL36AL	Liver	0.0000063
			Brain-nucleus accumbens	0.0000071
rs3117017	eQTLs	COL11A2	Thyroid	2.0 × 10-8
		HCG24	Brain-nucleus accumbens	5.0 × 10-25
			Brain-putamen	6.4 × 10-17
			Brain-cortex	3.0 × 10-14
			Brain-caudate	3.4 × 10-14
			Brain-frontal cortex	4.3 × 10-11
			Brain-anterior cingulate cortex	0.000022
			Brain-hippocampus	0.000025
		HLA-DOA	Whole blood	0.00005
		HLA-DPA1	Cells-cultured fibroblasts	0.000071
		HLA-DPB1	Testis	0.000028
		HLA-DPB2	Brain-nucleus accumbens	1.3 × 10-18
			Brain-caudate	2.4 × 10-13
			Brain-putamen	3.4 × 10-11
			Brain-cortex	3.5 × 10-8
			Brain-hypothalamus	3.6 × 10-7
			Brain-cerebellum	0.000057
		HSD17B8	Thyroid	1.0 × 10-13
			Muscle-skeletal	3.5 × 10-11
			Esophagus-muscularis	1.3 × 10-8
			Artery-tibial	5.6 × 10-7
			Esophagus-gastroesophageal junction	0.0000011
			Colon-sigmoid	0.0000018
			Heart-left ventricle	0.0000028
			Testis	0.0000032
			Adipose-visceral	0.000016
			Artery-aorta	0.000018
			Esophagus-mucosa	0.000029
			Skin-not sun exposed	0.00003
			Cells-cultured fibroblasts	0.000065
		RING1	Pancreas	0.0000059
		RPS18	Artery-tibial	0.000032
			Whole blood	0.000084
		WDR46	Lung	0.000018
	sQTLs	COL11A2	Thyroid	3.5 × 10-8
			Brain-spinal cord	9.0 × 10-7
			Pituitary	0.0000084
		HLA-DPB1	Skin-sun exposed (lower leg)	6.6 × 10-7
			Muscle-skeletal	8.5 × 10-7
			Skin-not sun exposed (suprapubic)	8.6 × 10-7
		HLA-DPB2	Brain-cerebellum	1.9 × 10-12
			Skin-sun exposed (lower leg)	6.6 × 10-7
			Muscle-skeletal	8.5 × 10-7
			Skin-not sun exposed (suprapubic)	8.6 × 10-7
			Brain-spinal cord	0.000004
			Colon-transverse	0.000014
			Artery-tibial	0.000063
			Testis	0.00012
rs75836320	-	-	-	-
rs362071	eQTLs	MED15	Artery-tibial	3.1 × 10-13
			Nerve-tibial	1.2 × 10-11
			Esophagus-muscularis	5.4 × 10-11
			Lung	1.4 × 10-9
			Adipose-subcutaneous	6.5 × 10-9
			Thyroid	8.2 × 10-9
			Spleen	1.4 × 10-8
			Whole blood	3.6 × 10-8
			Artery-aorta	9.0 × 10-8
			Colon-transverse	1.2 × 10-7
			Adrenal gland	2.0 × 10-7
			Adipose-visceral	5.0 × 10-7
			Prostate	5.8 × 10-7
			Liver	9.7 × 10-7
			Esophagus-gastroesophageal junction	0.0000046
			Pancreas	0.0000063
			Skin-sun exposed (lower leg)	0.000015
			Cells-cultured fibroblasts	0.000052
	sQTLs	KLHL22	Skin-sun exposed (lower leg)	0.000003
			Skin-not sun exposed (suprapubic)	0.0000049
		MED15	Muscle-skeletal	3.0 × 10-7

eQTLs: Expression quantitative trait loci; sQTLs: Splicing quantitative trait loci.