Table 1 New signals for glycemic traits discovered in GWAS meta-analysis of RG levels in up to 459,772 individuals of European ancestries without diabetes

From: GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification

Signal	Nearest gene(s)	Variants	Chr	Position	Type/model	Alleles	EAF	Effect	SE	P value	P het	n
EUR	KDM4A	rs3791033	1	44,134,077	lead/7	T/C	0.67	−0.0017	0.00031	3.9 × 10⁻⁸	0.58	455,267
EUR	FAM46C	rs1966228	1	118,144,332	additional/5	A/G	0.75	0.0032	0.00034	1.3 × 10⁻²⁰	0.98	412,368
EUR	FAM46C	rs17656269	1	118,162,139	lead/7	T/C	0.33	0.0030	0.00032	4.3 × 10⁻²¹	0.075	455,647
EUR^a	EDEM3	rs78444298	1	184,672,098	lead/5	A/G	0.020	0.0076	0.0011	2.8 × 10⁻¹²	0.68	398,925
EUR	ACVR1C	rs58288813	2	158473008	lead/5	T/C	0.95	0.0037	0.00066	2.3 × 10⁻⁸	0.0073	415,629
EUR	ACVR1C	rs2848657	2	158495349	additional/7	A/T	0.13	0.0026	0.00044	2.4 × 10⁻⁹	0.13	454,031
EUR	RBMS1	rs12692596	2	161,265,910	lead/7	T/C	0.37	0.0019	0.00030	1.2 × 10⁻⁹	0.84	457,182
EUR^a	NEUROD1	rs8192556	2	182,542,998	lead/7	T/G	0.024	0.0053	0.00096	3.0 × 10⁻⁸	0.50	418,468
EUR	CACNA2D3	rs34222465	3	55,123,055	lead/1	A/G	0.56	−0.0019	0.00030	3.7 × 10⁻¹⁰	0.055	418,498
EUR	TRIM59, KPNA4	rs9799314	3	160,082,071	lead/7	T/C	0.47	0.0018	0.00030	1.1 × 10⁻⁹	0.025	439,182
EUR	MECOM	rs73174306	3	169,194,244	lead/5	A/T	0.96	−0.0059	0.00074	1.3 × 10⁻¹⁵	1.00	393,841
EUR	LCORL	rs1503884	4	18,207,538	lead/5	T/G	0.56	−0.0018	0.00030	8.8 × 10⁻¹⁰	0.65	414,134
EUR	SCD5	rs4693043	4	83,563,582	lead/7	A/G	0.14	0.0023	0.00042	2.9 × 10⁻⁸	0.66	456,696
EUR	ADRB2	rs71584073	5	148,149,418	lead/5	T/C	0.92	0.0038	0.00056	1.7 × 10⁻¹¹	0.91	398,925
EUR	SYNGAP1	rs9461856	6	33,395,199	lead/1	A/G	0.49	−0.0017	0.00030	4.9 × 10⁻⁹	0.29	436,654
EUR	ARMC2, SESN1	rs118126621	6	109,304,170	lead/5	A/G	0.025	0.0055	0.00098	2.3 × 10⁻⁸	0.029	393,841
EUR	PEX7	rs7756291	6	137,235,325	lead/7	T/C	0.55	−0.0016	0.00030	4.4 × 10⁻⁸	0.47	434,769
EUR	POP7, EPO	rs221798	7	100,287,495	lead/5	C/G	0.11	−0.0030	0.00047	7.1 × 10⁻¹¹	0.78	415,738
EUR	PRKAR2B	rs3801969	7	106,711,492	lead/1	T/G	0.44	0.0017	0.00030	1.2 × 10⁻⁸	0.47	458,102
EUR	A1CF	rs61856594	10	52,637,925	lead/7	A/G	0.70	0.0022	0.00032	7.3 × 10⁻¹²	0.59	451,966
EUR	ADRA2A	rs11195538	10	113,117,650	additional/5	T/C	0.93	0.0031	0.00060	2.3 × 10⁻⁷	0.21	403,260
EUR	TCF7L2	rs144155527	10	114,737,633	additional/5	T/C	0.019	−0.0061	0.0011	3.5 × 10⁻⁸	0.33	398,925
EUR	USP47	rs11022029	11	11,806,317	lead/5	T/C	0.85	0.0023	0.00042	3.4 × 10⁻⁸	0.75	414,134
EUR	PDE3B	rs141521721	11	14,763,828	lead/5	A/C	0.024	0.0054	0.00098	2.6 × 10⁻⁸	0.38	398,925
EUR	OR4A5	rs72913090	11	50,653,357	lead/5	A/C	0.92	0.0033	0.00055	2.7 × 10⁻⁹	1.0	380,422
EUR	TRIM48	rs150587121	11	55,036,391	lead/5	T/C	0.91	0.0030	0.00054	3.3 × 10⁻⁸	0.12	396,388
EUR	OR8K3, OR8K1	rs2170441	11	56,095,739	lead/5	A/G	0.078	−0.0032	0.00056	9.5 × 10⁻⁹	0.57	398,925
EUR	CCND2	rs3217791	12	4,384,669	additional/7	T/C	0.074	−0.0032	0.00059	8.2 × 10⁻⁸	0.69	393,841
EUR	SOX5	rs12581677	12	24,060,732	lead/5	A/G	0.91	0.0032	0.00053	3.1 × 10⁻⁹	0.10	414,063
EUR	MANSC4, KLHL42	rs11049144	12	27,931,511	lead/5	A/C	0.22	−0.0022	0.00036	1.2 × 10⁻⁹	0.012	413,498
EUR	RNF6	rs12874929	13	26,781,607	lead/1	A/G	0.77	−0.0026	0.00035	5.5 × 10⁻¹⁴	1.0	456,162
EUR	SPRY2	rs4884144	13	80,678,136	lead/5	A/G	0.67	0.0019	0.00032	1.2 × 10⁻⁹	0.38	411,619
EUR	HERC1	rs67507374	15	64,038,340	additional/5	A/T	0.31	−0.0024	0.00032	8.9 × 10⁻¹⁴	0.28	415,015
EUR	HNF1B	rs10908278	17	36,099,952	lead/5	A/T	0.52	−0.0019	0.00030	2.3 × 10⁻¹⁰	0.39	398,925
EUR^b	NMT1	rs2239923	17	43,176,804	lead/1	T/C	0.29	0.0020	0.00030	1.1 × 10⁻⁹	0.54	458,104
EUR	WIPI1	rs2952295	17	66,447,421	lead/5	A/T	0.23	0.0024	0.00035	4.5 × 10⁻¹²	0.14	398,925
EUR	SKA1, MAPK4	rs2957989	18	48,075,733	lead/1	A/G	0.82	0.0021	0.00039	3.4 × 10⁻⁸	0.67	437,935
EUR	RALY	rs7274168	20	32,435,978	lead/1	T/C	0.48	0.0018	0.00030	4.5 × 10⁻⁹	0.75	443,728
EUR	HNF4A	rs2267850	20	43,524,963	lead/7	T/C	0.27	−0.0021	0.00033	6.2 × 10⁻¹⁰	0.92	437,057
EUR	TSHZ2	rs2255805	20	51,627,634	lead/5	T/C	0.58	−0.0019	0.00030	1.5 × 10⁻¹⁰	0.90	414,134
EUR	STX16–NPEPL1	rs61285514	20	57,283,828	lead/7	A/G	0.77	0.0021	0.00035	2.3 × 10⁻⁹	0.24	451,642
EUR	EEF1A2, PPDPF	rs6122466	20	62,139,177	lead/5	A/G	0.86	−0.0026	0.00043	7.8 × 10⁻¹⁰	0.70	405,111

A lead signal was annotated as ‘EUR’ if it reached genome-wide significance (P < 5.0 × 10⁻⁸) in the meta-analysis of European ancestry cohorts in either of our two models of interest with adjustment for age, sex with or without time since last meal (where available) along with the exclusion of extreme hyperglycemia (RG > 20 mmol l⁻¹) or in their combination. Additional distinct signals with a region-wide threshold of P ≤ 1.0 × 10⁻⁵ are also reported. Effects and P values reported are from the model indicated in column ‘type/model’ (1, AS20; 5, AST20; 7, AS20 + AST20). Heterogeneity among studies was assessed using the I² index.
^aNonsynonymous variants.
^bSynonymous variants.
Alleles, effect/other; Chr, chromosome; EAF, effect allele frequency (frequency of allele, for which beta is reported); EUR, individuals of European ancestry; Pos, position GRCh37.

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Table 1 New signals for glycemic traits discovered in GWAS meta-analysis of RG levels in up to 459,772 individuals of European ancestries without diabetes

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