Low trait locus penetrances

The relative risks associated with particular alleles for complex diseases are seldom much above two-fold.

ID Disease/outcome	Gene (polymorphism), contrast	Sample size*	OR (F) (95% CI)	OR (R) (95% CI)	p Het		(number of studies)
1 Myocardial infarction	ACE (insertion/deletion), DD vs DI+II	18 664 (15)	1·20 (1·10­1·31)	1·28 (1·09­1·50)	0·001
2 Ischaemic heart desease	ACE (insertion/deletion), DD vs DI+II	21 876 (17)	1·16 (1·08­1·25)	1·20 (1·06­1·36)	0·004
3 ICVD	ACE (insertion/deletion), DD vs DI+II	11 394 (6)	1·18 (1·01­1·37)	1·21 (0·98­1·50)	0·187
4 Poor clozapine response	HTR2A (102T/C), CC vs CT+TT	733 (6)	1·64 (1·18­2·28)	1·65 (1·19­2·29)	0·514
5 Poor clozapine response	HTR2A (H452Y), YY vs HY+HH	676 (5)	5·55 (1·15-26·8)	3·37 (0·97­11·6)	0·941
6 Vascular disease	MTHFR (677C/T), TT vs CC	6947 (23)	1·08 (0·95­1·22)	1·12 (0·92­1·37)	0·001
7 Lung cancer	CYP2D6 (deficient oxidation),	5162 (14)	0·67 (0·53­0·84)	0·63 (0·42­0·93)	0·013
	poor metabolisers vs others
8 Dementia in Down's syndrome	APOE (2/3/4), allele 2 vs 3+4	1130 (9)	0·41 (0·22­0·78)	0·45 (0·17­1·17)	0·044
9 Schizophrenia	DRD3 (Bal1), 11+22 vs 12	5121 (25)	1·07 (0·95­1·20)	1·08 (0·95­1·23)	0·204
10 Bipolar affective disorder	MAOA (Fnu4HI), allele 1 vs 2	962 (3)	1·30 (0·96­1·75)	1·42 (0·82­2·46)	0·052
11 Bipolar affective disorder	MAOA (CA), allele 122 vs others	1932 (7)	0·95 (0·75­1·21)	0·95 (0·69­1·31)	0·115
12 Bipolar affective disorder	TH (tetranucleotide repeat), allele 1 vs others	2901 (8)	0·92 (0·78­1·08)	0·97 (0·74­1·26)	0·019
13 Unipolar affective disorder	TH (tetranucleotide repeat), allele 1 vs others	1128 (3)	1·17 (0·91­1·51)	1·17 (0·91­1·51)	0·370
14 NIDDM	KCNJ11/KIR6.2-BIR (E23K), KK vs EK+EE	888 (4)	1·94 (1·30­2·88)	1·93 (1·29­2·87)	0·777
15 Lung cancer	GSTM1 (gene deletion), null/null vs others	9724 (21)	1·17 (1·07­1·27)	1·18 (1·04­1·34)	0·007
16 Lung cancer	CYP1A1 (4889A/G), GG vs AA+AG	2392 (6)	1·45 (0·80­2·62)	2·07 (0·71­6·08)	0·106
17 Lung cancer	CYP1A1 (MspI), +/+ vs others	4263 (12)	1·21 (0·87­1·70)	1·26 (0·84­1·89)	0·294
18 Myocardial infarction	SERPINE1/PAI-1 promoter (4G/5G),	3381 (9)	1·32 (1·15­1·52)	1·55 (1·16­2·08)	0·001
	4G/4G vs 5G/5G
19 Parkinson's disease	CYP2D6 (1934G-A), allele 4 vs others	7029 (14)	1·17 (1·03­1·32)	1·18 (1·00­1·40)	0·094
20 Essential hypertension	AGT (M235T), allele T235 vs M235	4698 (6)	1·22 (1·06­1·42)	1·44 (1·04­2·00)	0·002
21 Cancer	HRAS/HRAS1 (rare alleles)	8542 (24)	1·91 (1·62­2·27)	1·84 (1·54­2·21)	0·364
	rare vs common alleles
22 Left ventricular hypertrophy	ACE (insertion/deletion), allele D vs I	8186 (12)	1·08 (0·97­1·21)	1·13 (0·95­1·33)	0·085
23 Bladder cancer	NAT2 (slow acetylation alleles),	5836 (20)	1·38 (1·23­1·55)	1·43 (1·20­1·71)	0·010
	slow/slow vs others
24 ICVD	APOE (2/3/4), allele 4 vs others	3632 (9)	1·71 (1·38­2·11)	1·69 (1·37­2·09)	0·449
25 Non­syndromic cleft lip	TGFA (TaqI), allele 2 vs 1	5272 (9)	1·50 (1·23­1·82)	1·58 (1·13­2·21)	0·012
26 Alcoholism	DRD2 (TaqIA), allele A1 vs A2	3826 (15)	1·50 (1·26­1·79)	1·60 (1·19­2·15)	0·002
27 Ischaemic stroke	ACE (insertion/deletion), DD vs DI+II	2160 (6)	1·42 (1·16­1·74)	1·58 (1·11­2·25)	0·022
28 Diabetic nephropathy	ACE (insertion/deletion), II vs ID+DD	5393 (20)	0·73 (0·63­0·83)	0·68 (0·55­0·84)	0·006
29 Neural tube defects	MTHFR (677C/T), TT vs CT+CC	3880 (13)	1·68 (1·38­2·05)	1·67 (1·26­2·23)	0·105
30 Neural tube defects	MTHFR (677C/T) mother, TT vs CT+CC	1955 (8)	1·95 (1·44­2·65)	1·98 (1·46­2·68)	0·844
31 Neural tube defects	MTHFR (677C/T) father, TT vs CT+CC	950 (5)	1·09 (0·62­1·93)	1·15 (0·65­2·05)	0·568
32 Ischaemic heart disease	APOE (2/3/4),	8 962 (9)	1·27 (1·14­1·42)	1·39 (1·11­1·73)	0·001
	4/3+4/2+4/4 vs 3/3
33 Ischaemic heart disease	LPL (D9N), ND vs DD	2 022 (3)	1·37 (0·81­2·33)	1·36 (0·80­2·32)	0·861
34 Ischaemic heart disease	LPL (N291S), SN vs NN	13 115 (4)	1·15 (0·91­1·46)	1·15 (0·91­1·46)	0·996
35 Ischaemic heart disease	LPL (S447X), XS vs SS	4067 (5)	0·84 (0·70­1·00)	0·84 (0·70­1·00)	0·969
36 Alcoholic liver disease	CYP2E/CYP2E1 (RsaI), allele c2 vs others	4178 (9)	1·54 (1·04­2·30)	1·41 (0·78­2·55)	0·119
37 Myocardial infarction	FGB/FGB promoter (455G/A), AA vs GG	1561 (3)	0·68 (0·47­0·99)	0·68 (0·47­1·00)	0·839
38 Myocardial infarction	F5 (1691G/A), AA+AG vs GG	5937 (12)	1·29 (1·03­1·61)	1·32 (1·03­1·70)	0·336
39 Myocardial infarction	F2 (20210G/A), AA+AG vs GG	5637 (7)	1·11 (0·79­1·56)	1·20 (0·80­1·80)	0·281
40 Ulcerative colitis	IL1RN (86-BP DUP), carriers of 2 vs others	2835 (8)	1·23 (1·04­1·45)	1·18 (0·88­1·57)	0·011
41 CAD	ITGB3 (L33P), A2A2 vs A1A2+A1A1	17 315 (31)	1·07 (1·00­1·14)	1·10 (0·99­1·21)	0·004
42 Fractures	COL1A1 (2046G/T), ss+Ss vs SS	3580 (13)	1·39 (1·17­1·65)	1·43 (1·13­1·81)	0·088
43 Bipolar disorder	DRD3 (Bal1), allele 1 vs allele 2	3392 (9)	1·01 (0·87­1·16)	1·01 (0·87­1·16)	0·545
44 Parkinson's disease	MAPT (allele A0), allele A0 vs others	2090 (5)	1·53 (1·23­1·91)	1·52 (1·22­1·90)	0·445
45 Bulimia	HTR2A (1438G/A), allele A vs G	1126 (3)	1·32 (1·04­1·69)	1·33 (1·04­1·69)	0·427
46 Anorexia nervosa	HTR2A (1438G/A), allele A vs G	3698 (7)	1·36 (1·19­1·57)	1·42 (1·05­1·93)	<0·001
47 Bladder cancer	GSTM1 (gene deletion), null/null vs others	4724 (15)	1·50 (1·32­1·71)	1·54 (1·27­1·86)	0·037
48 SLE nephritis	FCGR2A (R131H), RR vs RH+HH	2801 (24)	1·12 (0·93­1·35)	1·11 (0·88­1·41)	0·123
49 SLE	FCGR2A (R131H), RR vs RH+HH	4708 (21)	1·29 (1·12­1·48)	1·29 (1·10­1·52)	0·218
50 Parkinson's disease	COMT (V158M), MM+MV vs VV	964 (3)	1·31 (0·84­2·04)	1·37 (0·68­2·76)	0·097
51 Recurrent early pregnancy loss	MTHFR (677C/T), TT vs CT+CC	1097 (6)	1·37 (0·95­1·98)	1·31 (0·78­2·20)	0·146
52 Alzheimer's disease	MAPT (extended haplotypes),	3377 (7)	1·03 (0·89­1·19)	1·03 (0·89­1·20)	0·377