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PDGene Top Results

Status:

Updated 20 August 2010; ***Please consult the "Top Results Methods" for details on new ranking procedure***

Ranking based on HuGENet interim guidelines for the assessment of genetic association studies
#	Gene	Ethnicity	Polymorphism	N minor (Grade)	I² (Grade)	Bias Reason (Grade)	Overall Grade
1	SNCA	All	rs11931074	28269 (A)	n.a. (A)	(A)	A
2	MAPT/STH	All	rs199533	7354 (A)	n.a. (A)	(A)	A
3	NUCKS1	All	rs823128	6194 (A)	n.a. (A)	(A)	A
4	PM20D1	All	rs11240572	7718 (A)	n.a. (A)	(A)	A
5	SLC41A1	Asian	rs823156	7343 (A)	n.a. (A)	(A)	A
6	BST1	Asian	rs4538475	15523 (A)	n.a. (A)	(A)	A
7	LRRK2	Asian	rs7304279	3496 (A)	n.a. (A)	(A)	A
8	USP24	All	rs13312	1288 (A)	0 (A)	(A)	A
9	SLC6A3	Caucasian	rs72527228	1172 (A)	0 (A)	(A)	A
10	GBA	All	GBA_N370S	563 (B)	n.a. (A)	(A)	B
11	SLC45A3	Asian	rs16856139	5601 (A)	33 (B)	(A)	B
12	SOD2	Asian	rs4880	287 (B)	0 (A)	(A)	B
13	MTHFR	Asian	rs1801133	335 (B)	0 (A)	(A)	B
14	BDNF	All	rs11030104	3566 (A)	0 (A)	Low OR (C)	C
15	PDXK	All	rs2010795	10262 (A)	29 (B)	Low OR (C)	C
16	GWA_7p14.2	All	rs17329669	4232 (A)	35 (B)	Low OR (C)	C
17	DRD3	All	rs6280	7089 (A)	0 (A)	Low OR (C)	C
18	APOE	All	rs7412	2371 (A)	0 (A)	Low OR, Regr (C)	C
19	UCHL1	All	rs5030732	11365 (A)	33 (B)	Low OR (C)	C
20	GWA_2q36.3	Caucasian	rs10200894	2517 (A)	28 (B)	Low OR (C)	C
21	GSTM1	Caucasian	GSTM1*0	3465 (A)	0 (A)	Low OR (C)	C
22	PINK1	Caucasian	rs1043424	5171 (A)	13 (A)	Low OR, Regr (C)	C
23	FGF20	All	rs12718379	5718 (A)	0 (A)	Low OR (C)	C
24	CYP2D6	All	rs3892097	4469 (A)	41 (B)	Low OR, Regr (C)	C
25	PARK2	All	rs1801582	1360 (A)	63 (C)	HWE (C)	C
26	GLIS1	All	rs797906	5932 (A)	0 (A)	Low OR (C)	C
27	HLA-DRA	All	rs3129882	11076 (A)	83 (C)	(A)	C
28	MAOB	All	rs1799836	10594 (A)	46 (B)	Low OR (C)	C
29	CALB1	All	rs1805874	5855 (A)	44 (B)	Low OR, Regr (C)	C
30	FARP1	All	rs2282048	5484 (A)	25 (B)	Low OR, F, HWE (C)	C
31	LRP8	All	rs5174	6645 (A)	0 (A)	Low OR (C)	C
32	DRD2	All	rs1079597	1689 (A)	21 (A)	F (C)	C

Each nominally significant meta-analysis in PDGene is graded based on HuGENet (Human Genome Epidemiology Network) interim criteria for the assessment of cumulative evidence of genetic associations (Ioannidis et al, 2008; Khoury et al, 2009). These criteria take into account amount of evidence (i.e. sample size, measured as "N minor"), consistency of replication (i.e. heterogeneity across studies, measured as "I2"), and protection from bias ("Bias reason").

1. Amount of evidence: grade "A" is assigned when the total number of minor alleles of cases and controls combined in the meta-analyses exceeds 1,000, "B" when it is between 100 and 1,000, and "C" when it is less than 100.
2. Consistency of replication: grade "A" is assigned for I2 point estimates <25%, "B" for I2 values of 25–50%, and "C" for I2 values >50%. This criterion does not apply to meta-analyses with a P-value <1x10-7 after exclusion of the initial studie(s), as described in Khoury et al, 2009.
3. Protection from bias: the following potential reasons for bias in the meta-analysis results are systematically assessed: summary OR <1.15 ("Low OR"), loss of significance after exclusion of first study ("F"), loss of significance after exclusion of studies with deviations from Hardy-Weinberg equilibrium in control populations ("HWE"), or evidence for positive publication bias using a modified regression test ("Regr"). If none of the latter conditions are met grade "A" is assigned, otherwise grade "C".

Overall epidemiological credibility is graded as "A" (=strong) if associations received three A grades, "B" (=moderate) if they received at least one B grade but no C grades, and "C" (=weak) if they received a C grade in any of the three assessment criteria. Loci with the same grade are ordered by P-value. For more details see "Top Results Methods" and reference below.