Survival bias and drug interaction can attenuate cross-sectional case-control comparisons of genes with health outcomes. An example of the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism and coronary heart disease

Table 1 Studies of KIF6 and CHD or CVD risk.

	Events/Total			Risk allele frequency	Hazard ratios
	Arg/Arg	Arg/Trp	Trp/Trp		Arg/Arg	Arg/Trp	Arg carriers
CARE[6]¹	16/155	82/636	44/542	35.5	1.33 (P = 0.33)	1.54 (P = 0.02)	1.50 (P = 0.03)
WOSCOPS[6]²	35/94	137/341	104/360	33.3	1.48 (P = 0.11)	1.56 (P = 0.006)	1.55 (P = 0.005)
ARIC [13]³	144/1252	474/4363	382/3926	36.0	1.22 (P = 0.03)	1.12 (P = 0.09)	(P = 0.02)⁸
Woman's Health Study [11]⁴	95/3249	349/11831	256/10203	36.3	1.25 (P = 0.09)	1.23 (P = 0.02)	1.24 (P = 0.01)
PROSPER with vascular disease [8]⁵	25/159	119/573	83/514	35.8	1.02 (P = 0.95)	1.36 (P = 0.03)	1.28 (P = 0.07)
PROSPER without vascular disease [8]⁵	13/209	70/759	69/668	36.0	0.64 (P = 0.15)	0.87 (P = 0.43)	0.82 (P = 0.23)
Heart Protection Study [9]⁶							1.17 (P = 0.2)
CHS-White [12]⁷							1.29 (P = 0.005)
CHS-Black [12]⁷							4.14 (P = 0.08)

¹ Secondary prevention of fatal and nonfatal myocardial infarction; ²Primary prevention of CHD death, nonfatal myocardial infarction, revascularization; ³ Primary definite, probable and silent myocardial infarctions, definite fatal CHD death, or coronary revascularization; ⁴Primary myocardial infarction or stroke, coronary revascularization, cardiovascular death; ⁵Primary or secondary prevention of CHD death, myocardial infarction, or revascularization; ⁶Major coronary events; ⁷Primary or secondary myocardial infarction (definite or probable nonfatal and definite fatal). ⁸Additive model.

ISSN: 1471-2350