Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

Eli A Stahl et.al

Nature genetics 2019 May 1

SHANK2 遺伝子は、ASD、精神薄弱等々関連論文が極めて多数あり、ヒトの精神に関連する遺伝子であることがほぼ確実な遺伝子。NCBIでの検索でも頭脳との関連が明確に示されており、一々論文を探す必要のないレベルでヒトの精神と関連していることが確実である。

PLEKHO1 13, snv-35=1
LMAN2L 13
SCN2A 50
TRANK1 48, snv-1=2
ITIH1 11
CD47 21
FSTL5 260 snv-1=1
ADCY2 138
SSBP2 115 snv-1=2
RIMS1 168 snv-1=1
POU3F2 2
RPS6KA2 243 snv-1=1
THSD7A 163 snv-1=1
SRPK2 126
MRPS33 6
ANK3 229 snv-1=2
ADD3 41
FADS2 28 snv-1=2
PACS1 78 snv-1=1
SHANK2 322 snv-1=1
CACNA1C 302 snv-1=1
STARD9 52 snv-1=1
ZNF592 26 snv-1=1
GRIN2A 167 snv-1=1
HDAC5 17
ZCCHC2 40

NCAN 17
STK4 44 snv-1=2

TFAP2B 11
DFNA5 23
SLC25A17 12
HLF 24
PHF15 18 snv-1=1 ODZ4 なし

Abstract

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1×10−4 in an additional 9,412 cases and 137,760 controls.

Here, we report the second GWAS of the PGC Bipolar Disorder Working Group, comprising 20,352 cases and 31,358 controls of European descent in a single, systematic analysis, with follow up of top findings in an independent sample of 9,412 cases and 137,760 controls.

RESULTS

GWAS of bipolar disorder (BD)

We performed a GWAS meta-analysis of 32 cohorts from 14 countries in Europe, North America and Australia (Supplementary Table 1A), totaling 20,352 cases and 31,358 controls of European descent (effective sample size 46,582).

Table 1.

Genome-wide significant bipolar disorder risk loci

Locus Name*1	Lead SNP	CHR	BP	A1/A2	GWAS Meta-analysis			Follow-up samples		Combined
Locus Name*1	Lead SNP	CHR	BP	A1/A2	Freq. A1	OR	P-value*2	OR	P-value*3	OR	P-value*2
A. Thirty loci with lead SNP P < 5×10−8 in combined GWAS+followup analysis

1,PLEKHO1	rs7544145	1	150,138,699	T/C	0.81	1.095	4.8E-07	1.064	0.010	1.085	4.8E-08
2,LMAN2L**	rs57195239	2	97,376,407	I/D	0.34	0.92	5.8E-09	0.96	0.030	0.93	3.8E-09
3,SCN2A	rs17183814	2	166,152,389	A/G	0.075	0.87	1.5E-07	0.89	0.0017	0.88	2.0E-09
4,[Intergenic]***	rs61332983	2	194,465,711	I/D	0.41	0.93	2.3E-08	0.95	0.0031	0.93	7.9E-10
5,TRANK1**	rs9834970	3	36,856,030	T/C	0.51	0.90	5.5E-14	0.98	0.15	0.93	5.7E-12
6,ITIH1**	rs2302417	3	52,814,256	A/T	0.49	0.92	4.9E-09	0.94	0.0012	0.93	6.6E-11
7,CD47	rs3804640	3	107,793,709	A/G	0.53	1.075	9.3E-08	1.044	0.016	1.065	2.0E-08
8,FSTL5	rs11724116	4	162,294,038	T/C	0.16	0.90	3.3E-08	0.95	0.031	0.92	2.4E-08
9,ADCY2**	rs200550695	5	7,587,236	I/D	0.82	0.91	1.2E-07	0.94	0.011	0.92	1.5E-08
10,SSBP2	rs10035291	5	80,796,368	T/C	0.68	1.081	1.1E-07	1.047	0.018	1.070	2.7E-08
11,RIMS1	rs57970360	6	72,519,394	D/I	0.44	1.066	3.1E-06	1.062	0.0016	1.064	3.5E-08
12,POU3F2**	rs2388334	6	98,591,622	A/G	0.52	0.93	8.6E-08	0.95	0.0051	0.94	4.0E-09
13,RPS6KA2	rs10455979	6	166,995,260	C/G	0.53	0.93	4.6E-08	0.97	0.046	0.94	4.3E-08
14,THSD7A	rs113779084	7	11,871,787	A/G	0.30	1.068	7.3E-06	1.095	2.9E-05	1.076	2.5E-09
15,SRPK2	rs73188321	7	105,048,158	T/C	0.33	0.92	7.0E-08	0.94	0.0015	0.92	1.1E-09
16,MRPS33	rs201231874	7	140,700,006	D/I	0.25	0.92	9.4E-08	0.93	0.0008	0.92	6.2E-10
17,ANK3**	rs10994318	10	62,125,856	C/G	0.057	1.151	4.5E-07	1.130	0.0021	1.145	6.8E-09
18,ADD3**	rs59134449	10	111,745,562	I/D	0.16	1.105	5.0E-08	1.059	0.017	1.090	1.2E-08
19,FADS2**	rs12226877	11	61,591,907	A/G	0.29	1.095	1.2E-08	1.062	0.0073	1.085	9.9E-10
20,PACS1	rs10896090	11	65,945,186	A/G	0.81	1.094	2.1E-07	1.062	0.0089	1.084	1.9E-08
21,PC	rs7122539	11	66,662,731	A/G	0.35	0.93	2.2E-07	0.96	0.015	0.94	3.8E-08
22,SHANK2	rs12575685	11	70,517,927	A/G	0.31	1.066	1.2E-05	1.088	5.7E-05	1.073	7.7E-09
23,CACNA1C**	rs10744560	12	2,387,099	T/C	0.34	1.087	2.9E-09	1.052	0.0086	1.076	3.6E-10
24,STARD9	rs4447398	15	42,904,904	A/C	0.12	1.112	1.1E-07	1.072	0.0079	1.099	9.4E-09
25,ZNF592	rs139221256	15	85,357,857	I/D	0.28	0.92	8.5E-09	0.97	0.082	0.93	2.7E-08
26,GRIN2A	rs11647445	16	9,926,966	T/G	0.65	0.93	1.2E-07	0.93	9.8E-05	0.93	1.1E-10
27,HDAC5	rs112114764	17	42,201,041	T/G	0.69	0.93	1.7E-06	0.94	0.0021	0.93	2.5E-08
28,ZCCHC2	rs11557713	18	60,243,876	A/G	0.29	1.074	1.2E-06	1.059	0.0038	1.069	3.6E-08
29,NCAN**	rs111444407	19	19,358,207	T/C	0.15	1.124	2.4E-10	1.040	0.075	1.097	1.3E-09
30,STK4	rs202012857	20	43,682,549	I/D	0.28	0.923	3.0E-07	0.942	0.0043	0.929	1.1E-08

B. Additional loci with lead SNP P < 5×10−8 in GWAS analysis

TFAP2B	rs55648125	6	50,816,718	A/G	0.90	0.89	4.9E-08	0.95	0.068	0.91	8.5E-08
DFNA5	rs17150022	7	24,771,777	T/C	0.88	0.89	2.7E-08	0.96	0.087	0.91	8.6E-08
SLC25A17	rs138321	22	41,209,304	A/G	0.50	1.083	4.7E-09	1.012	0.28	1.060	1.9E-07
HLF	rs884301	17	53,367,464	T/C	0.37	1.084	5.8E-09	1.013	0.26	1.061	2.1E-07
PHF15	rs329319	5	133,906,609	A/G	0.43	1.082	1.5E-08	1.019	0.18	1.061	2.1E-07
ODZ4**	rs73496688	11	79,156,748	A/T	0.14	1.11	1.0E-08	1.016	0.29	1.083	4.2E-07
[Intergenic]***	rs57681866	2	57,975,714	A/G	0.06	0.85	5.0E-08	0.97	0.23	0.89	1.2E-06
[Intergenic]***	rs13231398	7	110,197,412	C/G	0.11	0.89	3.4E-08	0.998	0.47	0.92	4.6E-06

*1Loci are numbered 1 to 30, ordered by genomic position, with previously reported gene name for published loci

*2P-values for GWAS and combined analyses are two-tailed, bold and underlined if p < 5×10−8.

*3P-values for follow-up are one-tailed based on the direction of effect in the discovery GWAS, bold and underlined if p < 0.05.

**Previously published and named loci. (Locus 12 would be named as Intergenic, nearest gene is POU3F2 691Kb.)

***Intergenic loci nearest genes: Locus 4 PCGEM1 824kb, Table 1B chr2 locus VRK2 298Kb, Table 1B chr7 IMMP2L 106Kb.

読書抜粋ノートブログ

⭕️Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

Abstract

RESULTS

GWAS of bipolar disorder (BD)

Table 1.

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