THE MOLECULAR GENETICS OF CIGARETTE SMOKING: DEMOGRAPHIC AND ENVIRONMENTAL COMPLEXITIESKyra Kanyas*, Ronnen H. Segman, Ofer Agid, Bernard Lerer.Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. As for other complex traits, there is considerable interest in identifying candidate genes that may predispose individuals to become addicted to cigarette smoking and influence intensity of smoking and difficulties with smoking cessation. Preliminary reports have implicated a number of candidate genes. We are studying a large sample of individuals phenotyped for details of lifetime cigarette use, psychiatric status and a variety of demographic, environmental and medical details - Normal controls (CON), n= 205; Major depression (MDD), n= 211; Bipolar disorder (BPD), n= 126; Schizophrenia (SCZ), n= 220. >100 subjects in each diagnostic group have DNA available and are being genotyped on a panel of candidate genes. Our approach has been to initially identify potential confounding variables in the larger sample. With regard to current smoking status, these include diagnosis (SCZ >BP >CON >UP, p<.000001); gender (M >F, p<.000001); ethnicity (Non-Ashkenazi >Ashkenazi, p<.0001); Marital status (Divorced >Single> >Married >Widowed, p<.000001); Religious observance (Non-religious >Ultra-Orthodox >Moderately religious, p=.01); Immigration status (Native Israeli >Veteran Immigrant >Recent Immigrant, p=.005); Educational level (Primary >Secondary >Higher, p=.006); Income (Low >Moderate/High; p=.005) and Younger age (p<.000001). In addition, there are specific factors in certain sub-groups (e.g. early parental loss in controls only). Identification of candidate genes that influence cigarette smoking will only be feasible in case control designs if a host of background and demographic variables are taken into account.
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