Jacqueline M. Otto

Risky Sex: Interactions among Ethnicity, Sexual Sensation Seeking, Sexual Inhibition, and Sexual Excitation

Rates of sexually transmitted infections, including HIV, vary across ethnic minority groups, yet few studies have evaluated sexual risk behaviors and their psychological correlates to determine if risk and protective factors vary by ethnicity. The purpose of the current study was to assess sexual sensation seeking (SSS), sexual inhibition (SIS1 and SIS2), and sexual excitation (SES) as correlates of risky sexual behaviors in 106 (55 male and 51 female) Asian Americans, African Americans, and Caucasian Americans. Results revealed that higher SSS was associated with more vaginal and anal sex partners. Further, the association between SSS and the number of anal sex partners was positive among Asian Americans and Caucasians, but non-significant among African Americans. SIS1 was positively associated with unprotected sex on the first date among Asian Americans and African Americans. However, the association was not significant for Caucasians. SIS2 was negatively associated with general unprotected sex, and SES was positively associated with the number of vaginal sex partners. Findings suggest that ethnicity plays an important moderating role in the relationship between sexual traits and risky sexual behaviors.

A New Decisional Balance Measure of Motivation to Change Among At-Risk College Drinkers

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 toward change (i.e., counts of pros of reducing drinking and cons of current drinking to all decisional balance fields). This studys 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 (K. B. Carey, M. P. Carey, S. A. Maisto, & J. M. Henson, 2006). Findings indicated partial support for convergent and discriminant validity of the DBP. Compared with Likert scale measures of decisional balance and readiness to change, DBP scores reflecting greater movement toward 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.

Evaluation of a brief web-based genetic feedback intervention for reducing alcohol-related health risks associated with ALDH2.

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 alcohol-related 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.

Assessing women's sexual arousal in the context of sexual assault history and acute alcohol intoxication.

INTRODUCTION Few studies have examined differences in womens sexual arousal based on sexual assault history (SAH) or in-the-moment alcohol intoxication. Only one has examined combined effects. Findings regarding the relationship between SAH and arousal are contradictory. AIM We aimed to determine the relationship between SAH, alcohol intoxication, and sexual arousal. METHODS Women were randomly assigned to an alcohol (target blood alcohol level = 0.10%) or control condition and categorized as having an SAH or not. After beverage administration, all women watched erotic films while genital arousal (vaginal pulse amplitude; VPA) was measured. Afterward, self-reported sexual arousal was measured. MAIN OUTCOME MEASURES Genital response was measured by VPA using vaginal photoplethysmography while watching erotic films. Self-reported sexual arousal was assessed after watching erotic films. RESULTS Women with an SAH had smaller increases in genital arousal in response to the films than women without an SAH. Intoxicated women had smaller increases in genital arousal than sober women. However, no differences for SAH or intoxication were found in self-reported arousal. CONCLUSION SAH and alcohol intoxication are associated with smaller increases in genital arousal compared to women without an SAH and sober women, suggesting that these co-occurring factors impact sexual arousal.

Evaluating a Cognitive Model of ALDH2 and Drinking Behavior

BACKGROUND Despite evidence for genetic influences on alcohol use and alcohol-related cognitions, genetic factors and endophenotypes are rarely incorporated in cognitive models of drinking behavior. This study evaluated a model of ALDH2 and drinking behavior stipulating cognitive factors and alcohol sensitivity as accounting for genetic influences on drinking outcomes. METHODS Participants were Asian-American young adults (n = 171) who completed measures of alcohol cognitions (drinking motives, drinking refusal self-efficacy, and alcohol expectancies), alcohol sensitivity, drinking behavior, and alcohol-related problems as part of a prospective study. Structural equation modeling (SEM) evaluated a model of drinking behavior that stipulated indirect effects of ALDH2 on drinking outcomes through cognitive variables and alcohol sensitivity. RESULTS The full model provided an adequate fit to the observed data, with the measurement model explaining 63% of the variance in baseline heavy drinking and 50% of the variance in alcohol-related problems at follow-up. Associations of ALDH2 with cognitive factors and alcohol sensitivity were significant, whereas the association of ALDH2 with drinking was not significant with these factors included in the model. Mediation tests indicated significant indirect effects of ALDH2 through drinking motives, drinking refusal self-efficacy, and alcohol sensitivity. CONCLUSIONS Results are consistent with the perspective that genetic influences on drinking behavior can be partly explained by learning mechanisms and implicate cognitive factors as important for characterizing associations of ALDH2 with drinking.

A Novel Tobacco Use Phenotype Suggests the 15q25 and 19q13 Loci May Be Differentially Associated with Cigarettes per Day and Tobacco-Related Problems

Introduction Tobacco use is associated with variation at the 15q25 gene cluster and the cytochrome P450 (CYP) genes CYP2A6 and CYP2B6. Despite the variety of outcomes associated with these genes, few studies have adopted a data-driven approach to defining tobacco use phenotypes for genetic association analyses. We used factor analysis to generate a tobacco use measure, explored its incremental validity over a simple indicator of tobacco involvement: cigarettes per day (CPD), and tested both phenotypes in a genetic association study. Methods Data were from the University of California, San Francisco Family Alcoholism Study (n = 1942) and a Native American sample (n = 255). Factor analyses employed a broad array of tobacco use variables to establish the candidate phenotype. Subsequently, we conducted tests for association with variants in the nicotinic acetylcholine receptor and CYP genes. We explored associations with CPD and our measure. We then examined whether the variants most strongly associated with our measure remained associated after controlling for CPD. Results Analyses identified one factor that captured tobacco-related problems. Variants at 15q25 were significantly associated with CPD after multiple testing correction (rs938682: p = .00002, rs1051730: p = .0003, rs16969968: p = .0003). No significant associations were obtained with the tobacco use phenotype; however, suggestive associations were observed for variants in CYP2B6 near CYP2A6 (rs45482602: ps = .0082, .0075) and CYP4Z2P (rs10749865: ps = .0098, .0079). Conclusions CPD captures variation at 15q25. Although strong conclusions cannot be drawn, these finding suggest measuring additional dimensions of problems may detect genetic variation not accounted for by smoking quantity. Replication in independent samples will help further refine phenotype definition efforts. Implications Different facets of tobacco-related problems may index unique genetic risk. CPD, a simple measure of tobacco consumption, is associated with variants at the 15q25 gene cluster. Additional dimensions of tobacco problems may help to capture variation at 19q13. Results demonstrate the utility of adopting a data-driven approach to defining phenotypes for genetic association studies of tobacco involvement and provide results that can inform replication efforts.

Association of the ALDH1A1*2 Promoter Polymorphism With Alcohol Phenotypes in Young Adults With or Without ALDH2*2

BACKGROUND Prior studies suggest a possible association of a promoter polymorphism in the ALDH1A1 gene ( ALDH1A1*2 ) with alcohol use or dependence. The aim of this study was to examine the association of ALDH1A1*2 with drinking behaviors in Asian young adults and to examine ALDH2 genotype as a potential moderator of these associations. METHODS Asian young adults (n = 951) were recruited from 2 college sites for studies of genetic associations with alcohol use behavior. Participants completed comprehensive background questionnaires on demographics and drinking behavior. Fingertip blood samples were obtained for DNA extraction and analysis. RESULTS Participants with the ALDH2*1/*2 genotype reported significantly lower levels (frequency and quantity) of drinking within the last 90 days, fewer numbers of heavy drinking episodes within the last 90 days, and lower lifetime maximum consumption levels compared with ALDH2*1/*1 participants. There were no significant main effects of ALDH1A1*2 on any drinking variables, nor was there a significant interaction between ALDH2 and ALDH1A1 genotypes on drinking outcomes. CONCLUSIONS The association of ALDH2*2 with reduced alcohol consumption replicates previous findings across numerous studies. Although ALDH1A1*2 was not associated with drinking levels, the lack of an ALDH1A1*2 effect in ALDH2*2 individuals is consistent with the only other study that has examined these associations in East Asian populations.

Genetic variation in the exome: Associations with alcohol and tobacco co-use.

Shared genetic factors represent one underlying mechanism thought to contribute to high rates of alcohol and tobacco co-use and dependence. Common variants identified by molecular genetic studies tend to confer only small disease risk, and rare protein-coding variants are posited to contribute to disease risk, as well. However, given that genotyping technologies allowing for their inclusion in association studies have only recently become available, the magnitude of their contribution is poorly understood. The current study examined genetic variation in protein-coding regions (i.e., the exome) for associations with measures of lifetime alcohol and tobacco co-use. Participants from the UCSF Family Alcoholism Study (N = 1,862) were genotyped using an exome-focused genotyping array, and assessed for DSM–IV diagnoses of alcohol and tobacco dependence and quantitative consumption measures using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism. Analyses included single variant, gene-based, and pathway-based tests of association. One EMR3 variant and a pathway related to genes upregulated in mesenchymal stem cells during the late phase of adipogenesis met criteria for statistical significance. Suggestive associations were consistent with previous findings from studies of substance use and dependence, including variants in the CHRNA5–CHRNA3–CHRNB4 gene cluster with cigarettes smoked per day. Further, several variants and genes demonstrated suggestive association across phenotypes, suggesting that shared genetic factors may underlie risk for increased levels of alcohol and tobacco use, as well as psychopathology more broadly, providing insight into our understanding of the genetic architecture underlying these traits.

Polygenic risk scores for cigarettes smoked per day do not generalize to a Native American population.

BACKGROUND Recent studies have demonstrated the utility of polygenic risk scores (PRSs) for exploring the genetic etiology of psychiatric phenotypes and the genetic correlations between them. To date, these studies have been conducted almost exclusively using participants of European ancestry, and thus, there is a need for similar studies conducted in other ancestral populations. However, given that the predictive ability of PRSs are sensitive to differences in linkage disequilibrium (LD) patterns and minor allele frequencies across discovery and target samples, the applicability of PRSs developed in European ancestry samples to other ancestral populations has yet to be determined. Therefore, the current study derived PRSs for cigarettes per day (CPD) from predominantly European-ancestry samples and examined their ability to predict nicotine dependence (ND) in a Native American (NA) population sample. METHOD Results from the Tobacco and Genetics Consortiums meta-analysis of genome-wide association studies of CPD were used to compute PRSs in a NA community sample (N=288). These scores were then used to predict ND diagnostic status. RESULTS The PRS was not significantly associated with liability for ND in the full sample. However, a significant interaction between PRS and percent NA ancestry was observed. Risk scores were positively associated with liability for ND at higher levels of European ancestry, but no association was observed at higher levels of NA ancestry. CONCLUSION These findings illustrate how differences in patterns of LD across discovery and target samples can reduce the predictive ability of PRSs for complex traits.