Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies

Nishizawa, Daisuke; Kasai, Shinya; Hasegawa, Junko; Sato, Naomi; Yamada, Hidetaka; Tanioka, Fumihiko; Nagashima, Makoto; Katoh, Ryoji; Satoh, Yasuo; Tagami, Megumi; Ujike, Hiroshi; Ozaki, Norio; Inada, Toshiya; Iwata, Nakao; Sora, Ichiro; Iyo, Masaomi; Yamada, Mitsuhiko; Kondo, Naoki; Won, Moo-Jun; Naruse, Nobuya; Uehara-Aoyama, Kumi; Itokawa, Masanari; Ohi, Kazutaka; Hashimoto, Ryota; Tanisawa, Kumpei; Arai, Tomio; Mori, Seijiro; Sawabe, Motoji; Naka-Mieno, Makiko; Yamada, Yoshiji; Yamada, Miki; Sato, Noriko; Muramatsu, Masaaki; Tanaka, Masashi; Irukayama-Tomobe, Yoko; Saito, Yuki C.; Sakurai, Takeshi; Hayashida, Masakazu; Sugimura, Haruhiko; Ikeda, Kazutaka

doi:10.1186/s13041-015-0142-x

Molecular Brain

Table 2 Top 50 candidate SNPs possibly associated with nicotine dependence (TDS score)

From: Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies

Rank	CHR	SNP	Position	Genotype^b(TDS ≥ 3)	Genotype^b(TDS < 3)	χ²	p	Related gene	Region	MAF	TFBS	Splicing	Polyphen
1	18	rs11662608	60876992	7/38/33	22/36/11	18.28	1.90E-05	CDH7	5′ flanking	0.44897959	-	-	-
2	2	rs10490099	58991504	6/40/33	0/19/50	16.33	5.33E-05	LOC730134	3′ flanking	0.23986486	-	-	-
3	13	rs17056451	37163539	8/44/24	2/22/45	16.24	5.59E-05	TRPC4	intron	0.29655172	-	-	-
4	4	rs13112895	60509294	18/40/21	5/24/40	16.17	5.80E-05	LOC644419	5′ flanking	0.37162162	-	-	-
5	9	rs10973120	36885382	5/20/54	9/38/22	15.88	6.76E-05	PAX5	intron	0.29054054	-	-	-
6	18	rs611411	60899889	26/43/10	10/31/28	15.82	6.95E-05	CDH7	5′ flanking	0.49324324	-	-	-
7	18	rs176136	60936692	18/43/18	5/28/36	15.61	7.80E-05	CDH7	5′ flanking	0.39527027	-	-	-
8	18	rs176121	60958616	14/42/23	4/23/42	15.28	9.28E-05	CDH7	5′ flanking	0.34121622	-	-	-
9	2	rs985162	129883821	10/44/25	0/29/40	15.18	9.76E-05	LOC402102	5′ flanking	0.31418919	-	-	-
10	5	rs1366589	84922599	11/35/33	4/12/53	15.17	9.81E-05	LOC645181	3′ flanking	0.26013514	-	-	-
11	18	rs12962611	18303667	5/47/27	0/25/44	15.1	1.02E-04	CTAGE1	5′ flanking	0.27702703	-	-	-
12	1	rs909530	169349798	16/46/17	4/31/34	15.06	1.04E-04	FMO3	syn^a	0.39527027	-	+	-
13	1	rs12032382	207272695	0/10/69	0/28/41	15.05	1.05E-04	LOC391157	5′ flanking	0.12837838	-	-	-
14	13	rs9532107	37187961	2/24/53	13/28/28	15.01	1.07E-04	TRPC4	intron	0.27702703	-	-	-
15	5	rs7719216	8023898	3/20/56	7/36/26	14.97	1.09E-04	MTRR	3′ flanking	0.25675676	-	-	-
16	4	rs923665	38214103	0/5/72	1/20/46	14.96	1.10E-04	NULL	3′ flanking	0.09375	-	-	-
17	15	rs28716882	21552860	3/28/48	0/8/61	14.94	1.11E-04	NDN	5′ flanking	0.14189189	-	-	-
18	2	rs875063	111529556	10/32/37	20/37/12	14.92	1.12E-04	ACOXL	intron	0.43581081	-	-	-
19	4	rs13144500	183475934	1/9/69	3/26/40	14.91	1.13E-04	ODZ3	intron	0.14527027	-	-	-
20	6	rs1772253	24528213	4/35/40	0/14/55	14.76	1.22E-04	MRS2L	intron	0.19256757	-	-	-
21	4	rs2866688	78968066	4/38/37	2/11/55	14.74	1.24E-04	CNOT6L	5′ flanking	0.20748299	-	-	-
22	12	rs17120420	56856068	18/44/16	4/34/31	14.45	1.44E-04	LOC338805	5′ flanking	0.41496599	-	-	-
23	17	rs16946572	12604902	7/30/42	17/35/17	14.32	1.54E-04	MYOCD	intron	0.38175676	-	-	-
24	18	rs4328535	70129056	12/39/28	0/28/41	14.16	1.68E-04	DKFZP781G0119	5′ flanking	0.30743243	+	-	-
25	16	rs10514585	81841839	7/43/29	22/35/12	14.16	1.68E-04	CDH13	intron	0.45945946	-	-	-
26	16	rs1379652	17304099	13/39/25	2/26/41	14.09	1.74E-04	XYLT1	intron	0.32534247	-	-	-
27	6	rs2496167	13450101	9/33/37	17/40/12	13.91	1.92E-04	TBC1D7	5′ flanking	0.4222973	-	-	-
28	11	rs623312	31864040	19/43/17	5/32/32	13.76	2.08E-04	LOC729605	5′ flanking	0.41554054	-	-	-
29	2	rs1403858	36566018	0/23/55	0/4/65	13.7	2.14E-04	CRIM1	intron	0.09183673	-	-	-
30	6	rs1591996	8291461	0/3/76	0/17/52	13.69	2.16E-04	SLC35B3	3′ flanking	0.06756757	-	-	-
31	9	rs4877369	89514689	8/26/45	19/30/20	13.65	2.20E-04	DAPK1	3′ flanking	0.37162162	-	-	-
32	16	rs17765854	64608419	21/43/15	7/31/31	13.63	2.22E-04	CDH5	5′ flanking	0.43918919	-	-	-
33	5	rs540375	152858920	2/23/54	0/5/64	13.59	2.27E-04	GRIA1	intron	0.10810811	-	-	-
34	16	rs2305689	69354016	10/30/39	19/36/14	13.48	2.41E-04	VAC14	intron	0.41891892	-	-	-
35	8	rs2975701	10147867	0/8/71	1/23/45	13.44	2.47E-04	MSRA	intron	0.11148649	-	-	-
36	2	rs1567852	174440084	1/22/56	0/4/65	13.33	2.61E-04	LOC344178	3′ flanking	0.09459459	-	-	-
37	7	rs1540893	143398486	18/31/29	2/26/41	13.27	2.70E-04	OR2A25	5′ flanking	0.32993197	+	-	-
38	1	rs6686733	4663049	4/28/47	0/10/59	13.26	2.71E-04	AJAP1	intron	0.15540541	-	-	-
39	13	rs9555699	109898019	3/28/48	12/33/24	13.12	2.92E-04	COL4A2	intron	0.30743243	-	-	-
40	15	rs10851750	63908644	6/26/47	17/29/23	13.03	3.06E-04	DENND4A	5′ flanking	0.34121622	-	-	-
41	10	rs520887	78720167	3/29/47	0/10/59	12.98	3.15E-04	KCNMA1	intron	0.15202703	-	-	-
42	6	rs573668	13446548	1/30/48	11/32/26	12.94	3.21E-04	TBC1D7	5′ flanking	0.29054054	-	-	-
43	20	rs4810359	40624749	10/30/39	1/16/52	12.84	3.39E-04	PTPRT	intron	0.22972973	-	-	-
44	12	rs10771391	27966867	23/41/15	6/36/27	12.84	3.40E-04	PTHLH	3′ flanking	0.45608108	-	-	-
45	14	rs2415449	37667678	13/41/25	2/28/39	12.83	3.42E-04	LOC729122	intron	0.33445946	-	-	-
46	7	rs3807171	37875304	11/39/29	2/23/44	12.82	3.43E-04	TXNDC3	intron	0.2972973	-	-	-
47	4	rs7667301	53395322	3/31/45	12/35/22	12.79	3.48E-04	RASL11B	5′ flanking	0.32432432	-	-	-
48	17	rs2188889	13178372	3/27/49	10/35/24	12.72	3.62E-04	HS3ST3A1	3′ flanking	0.2972973	-	-	-
49	5	rs6875661	54360379	9/37/33	16/43/10	12.65	3.76E-04	GZMK	intron	0.43918919	-	-	-
50	7	rs2058024	25742215	15/39/25	3/27/39	12.57	3.92E-04	LOC646588	5′ flanking	0.34459459	-	-	-

CHR, chromosome number; Position, chromosomal position (bp); Related gene, the nearest gene from the SNP site;
^a, coding region (synonymous polymorphism);
^b, distribution of genotype (homozygote of minor allele/heterozygote/homozygote of major allele);
MAF, minor allele frequency; TFBS, SNPs located at a transcription factor-binding site (TFBS) of a gene;
Splicing, SNPs located at exonic splicing enhancer (ESE) or exonic splicing silencer (ESS);
Polyphen, predicted possible impact of an amino acid substitution in nonsynonymous SNPs on the structure and function of a human protein by PolyPhen tool (http://genetics.bwh.harvard.edu/pph/)

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