Cotinine and 3-hydroxycotinine phenotypes were measured from frozen serum samples using liquid chromatography/tandem mass spectrometry (University of Toronto, prof. Rachel Tyndale’s laboratory) for the FinnTwin12, FinnTwin16, and YFS samples, as previously described [33], and using gas chromatograph-mass spectrometer (at the National Institute for Health and Welfare, Helsinki, Finland) for the FINRISK2007 sample, as previously described [34]; these assays for NMR were demonstrated to be fully concordant (R2 = 0.93, P<0.0001) [35]. Cotinine threshold of ≥10ng/ml was applied to restrict the analyses to regular smokers.