Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1–4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.

There is increasing interest in health interventions that incorporate genetic risk information. Although genetic feedback has been evaluated as an adjunct to smoking cessation interventions, its efficacy for reducing alcohol-related risks is unknown. The purpose of this study was to evaluate the feasibility, acceptability, and efficacy of a web-based alcohol intervention incorporating genetic feedback and risk information specific to ALDH2 genotype. The ALDH2*2 variant is associated with partial protection against alcohol dependence but confers significantly increased risk for alcohol-related cancers as a function of alcohol exposure. Two hundred Asian-American young adults were randomly assigned to receive web-based personalized genetic feedback or attention-control feedback. Genetic feedback included health risk information specific to alcoholrelated cancer or alcohol dependence, depending on genotype. Outcomes included postintervention drinking behavior and theoretical correlates of behavior change. Genetic feedback and risk information resulted in significant reductions in 30-day drinking frequency and quantity among participants with the ALDH2*1/*2 genotype. Genetic feedback was rated highly by participants and also showed some effects on theoretical correlates of behavior change. Results provide initial evidence of the feasibility, acceptability, and brief efficacy of web-based genetic feedback for reducing alcohol-related health risks associated with ALDH2 genotype. KeywordsAlcohol use; Aldehyde dehydrogenase; Intervention; Personalized feedback; Genetic feedback; Internet Correspondence to: Christian S. Hendershot, chender@unm.edu. NIH Public Access Author ManuscriptAnn Behav Med. Author manuscript; available in PMC 2011 August 1. The prospect of personalized medicine has generated substantial interest in behavioral interventions that incorporate genomic risk information [1,2]. Given the complexities of characterizing the genetic basis of common, multifactorial diseases, genome-based risk prediction remains a challenging goal. While genome-wide association studies are identifying risk alleles for common disorders [3], it is evident that these variants will be large in number and characterized by small associations with disease outcomes [4][5][6], currently yielding minimal predictive power above and beyond clinical indicators [7][8][9]. Additional challenges include the translation of empirically derived risk estimates into individualized interventions and evaluating whether and how genetic risk information might promote behavior change [10][11][12].To date, the incorporation of genetic feedback in substance use interventions is almost exclusive to studies of tobacco use. Two randomized trials evaluated the efficacy of genetic feedback for GSTM1, which encodes an enzyme involved in detoxifying environmental carcinogens and shows an association with lung cancer risk [13,14]. In one study, the addition of GSTM1 feedback to a multicomponent intervention resulted in greater abstinence rates 6 months ...

In this study, an open-ended decisional balance worksheet was used to elicit self-generated pros and cons of current drinking and reducing drinking, which were then quantified to create a decisional balance proportion (DBP) reflecting movement towards change (i.e., counts of pros of reducing drinking and cons of current drinking to all decisional balance fields). This study's goal was to examine the convergent, discriminant and predictive validity of the DBP as a measure of motivation to change. Participants were college students (N=143) who reported having engaged in weekly heavy, episodic drinking and who had participated in a larger randomized clinical trial of brief motivational interventions (Carey et al., 2006). Findings indicated partial support for convergent and discriminant validity of the DBP. Compared to Likert scale measures of decisional balance and readiness to change, DBP scores reflecting greater movement towards change best predicted reductions in heavy drinking quantity and frequency and experience of alcohol-related consequences -- although some of these effects decayed by the 12-month follow-up. Findings suggest that the DBP is a valid measure of motivation to change among at-risk college drinkers.

This study used an experimental paradigm to investigate the roles of sexual victimization history and alcohol intoxication in young women’s sexual-emotional responding and sexual risk taking. A nonclinical community sample of 436 young women, with both an instance of heavy episodic drinking and some HIV/STI risk exposure in the past year, completed childhood sexual abuse (CSA) and adolescent/adult sexual assault (ASA) measures. A majority of them reported CSA and/or ASA, including rape and attempted rape. After random assignment to a high alcohol dose (.10%) or control condition, participants read and projected themselves into an eroticized scenario of a sexual encounter involving a new partner. As the story protagonist, each participant rated her positive mood and her sexual arousal, sensation, and desire, and then indicated her likelihood of engaging in unprotected sex. Structural equation modeling analyses revealed that ASA and alcohol were directly associated with heightened risk taking, and alcohol’s effects were partially mediated by positive mood and sexual desire. ASA was associated with attenuated sexual-emotional responding and resulted in diminished risk taking via this suppression. These are the first findings indicating that, compared to non-victimized counterparts, sexually victimized women respond differently in alcohol-involved sexual encounters in terms of sexual-emotional responding and risk-taking intentions. Implications include assessing victimization history and drinking among women seeking treatment for either concern, particularly women at risk for HIV, and alerting them to ways their histories and behavior may combine to exacerbate their sexual risks.