Genetic risk-factors play as important a role in determining AD risk in women as in men. With the exception of certain sociocultural variables such as religious affiliation, the same personality, sociodemographic and axis I correlates of alcoholism risk are observed in women and men.

Self-reported CSA was associated with increased risk for adverse outcomes, controlling for family background. Family background risk factors also were associated with adverse outcome risk. Discordant pair analysis seems to provide an effective means of controlling for family background risk factors.

Context Previous studies have reported that early initiation of cannabis (marijuana) use is a significant risk factor for other drug use and drug-related problems. Objective To examine whether the association between early cannabis use and subsequent progression to use of other drugs and drug abuse/dependence persists after controlling for genetic and shared environmental influences. Design Cross-sectional survey conducted in 1996-2000 among an Australian national volunteer sample of 311 young adult (median age, 30 years) monozygotic and dizygotic same-sex twin pairs discordant for early cannabis use (before age 17 years). Main Outcome Measures Self-reported subsequent nonmedical use of prescription sedatives, hallucinogens, cocaine/other stimulants, and opioids; abuse or dependence on these drugs (including cannabis abuse/dependence); and alcohol dependence. Results Individuals who used cannabis by age 17 years had odds of other drug use, alcohol dependence, and drug abuse/dependence that were 2.1 to 5.2 times higher than those of their co-twin, who did not use cannabis before age 17 years. Controlling for known risk factors (early-onset alcohol or tobacco use, parental conflict/ separation, childhood sexual abuse, conduct disorder, major depression, and social anxiety) had only negligible effects on these results. These associations did not differ significantly between monozygotic and dizygotic twins. Conclusions Associations between early cannabis use and later drug use and abuse/ dependence cannot solely be explained by common predisposing genetic or shared environmental factors. The association may arise from the effects of the peer and social context within which cannabis is used and obtained. In particular, early access to and use of cannabis may reduce perceived barriers against the use of other illegal drugs and provide access to these drugs.

Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.

Background. Psychiatric history, familial history of suicide attempts, and certain traumatic life events are important predictors of suicidal thoughts and behaviour. We examined the epidemiology and genetics of suicidality (i.e. reporting persistent suicidal thoughts or a plan or suicide attempt) in a large community-based sample of MZ and DZ twin pairs.

The association between retrospectively reported childhood conduct disorder (CD) and a history of alcohol dependence (AD) was examined in a sample of 2,682 male, female, and unlike-sex adult twin pairs. There was a strong association between CD and AD in both men (tetrachoric r = .34, odds ratio = 2.8) and women (tetrachoric r = .53, odds ratio = 9.9). Genetic factors accounted for most of the association between CD and AD liability in men and women, with the remainder of the association being due to nonshared individual-specific environmental factors. Genetic inftuences common to CD and AD accounted for 17% and 35% of the genetic variation in AD liability in men and women, respectively, and accounted for 11 % and 23% of the total variation in AD liability in men and women, respectively. The results suggest that there are common genetic risk factors for CD and AD or that CD itself is an important genetically influenced risk factor for AD.

The etiology of CODdw:t disorder (CD) was examined retrospectively in a sample of 2,682 male.female, and un1ike-sex adult twin pairs from the community·based Australian 1Win Registec Modelfitting analyses indicated a substantial genetic intluence on risk for CD, accountiDg for 71<11 of the variance (95% confidence interval [CI] = 32-79<11). There was DOt a statistically sigui1icam effect of the shared environment in the best-fitting model of CD, but a modest effect of the shared environment on the risk for CD could not be rejected (95% CI = 0-32%). 1bemagoitude of genetic aDd environmental intluences for CD liability did not vary significantly for boys aDd girls. and the specific genetic aDd enviromnenta1 mechanisms important for the developmeat of CD appeared to be largely the san1e for both sexes. The fit of a multiple-thresbold model raises the possibility that CD may not necessarily be a discrete entity but rather an extreme of the normal variation in CODductdisordered behavior found in the general population.

The extent to which the genetic risk for alcohol dependence (AD) and conduct disorder (CD) and their common genetic risk overlap with genetic factors contributing to variation in dimensions of personality was examined in a study of 6,453 individuals from 3,383 adult male and female same-sex and unlike-sex twin pairs from the Australian Twin Registry. The associations between the personality dimensions of positive emotionality, negative emotionality, and AD and CD risk were modest, whereas the associations between behavioral undercontrol and AD and CD risk were substantially higher. Genetic influences contributing to variation in behavioral undercontrol accounted for about 40% of the genetic variation in AD and CD risk and about 90% of the common genetic risk for AD and CD. These results suggest that genetic factors contributing to variation in dimensions of personality, particularly behavioral undercontrol, account for a substantial proportion of the genetic diathesis for AD and most of the common genetic diathesis for AD and CD among both men and women.