Sherri L. Fisher

A genome-wide association study of alcohol dependence

Excessive alcohol consumption is one of the leading causes of preventable death in the United States. Approximately 14% of those who use alcohol meet criteria during their lifetime for alcohol dependence, which is characterized by tolerance, withdrawal, inability to stop drinking, and continued drinking despite serious psychological or physiological problems. We explored genetic influences on alcohol dependence among 1,897 European-American and African-American subjects with alcohol dependence compared with 1,932 unrelated, alcohol-exposed, nondependent controls. Constitutional DNA of each subject was genotyped using the Illumina 1M beadchip. Fifteen SNPs yielded P < 10−5, but in two independent replication series, no SNP passed a replication threshold of P < 0.05. Candidate gene GABRA2, which encodes the GABA receptor α2 subunit, was evaluated independently. Five SNPs at GABRA2 yielded nominal (uncorrected) P < 0.05, with odds ratios between 1.11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.

A genome-wide association study of DSM-IV cannabis dependence.

Despite twin studies showing that 50–70% of variation in DSM‐IV cannabis dependence is attributable to heritable influences, little is known of specific genotypes that influence vulnerability to cannabis dependence. We conducted a genome‐wide association study of DSM‐IV cannabis dependence. Association analyses of 708 DSM‐IV cannabis‐dependent cases with 2346 cannabis‐exposed non‐dependent controls was conducted using logistic regression in PLINK. None of the 948 142 single nucleotide polymorphisms met genome‐wide significance (P at E–8). The lowest P values were obtained for polymorphisms on chromosome 17 (rs1019238 and rs1431318, P values at E–7) in the ANKFN1 gene. While replication is required, this study represents an important first step toward clarifying the biological underpinnings of cannabis dependence.

Return of individual genetic results in a high-risk sample: enthusiasm and positive behavioral change

Purpose:The goal of this study was to examine participant responses to disclosure of genetic results in a minority population at high risk for depression and anxiety.Methods:Eighty-two subjects in a genetic study of nicotine dependence were offered personalized genetic results. All were nicotine-dependent and 64% self-identified as African American. Pathway Genomics was used to evaluate genetic risks for five complex diseases. Participants returned 4–8 weeks after enrollment for in-person genetic counseling interviews and evaluation of baseline measures. A telephone follow-up was performed 4–8 weeks later to assess responses to results.Results:Fifty of the 82 subjects (61%) were interested in receiving genetic results. These participants had multiple risk factors, including high baseline measures of depression (66%) and anxiety (32%), as well as low rates of employment (46%), adequate health literacy (46%), and health insurance (45%). Pathway Genomics reported “increased risk” for at least one disease in 77% of subjects. Ninety-five percent of participants reported that they appreciated the genetic results, and receiving these results was not associated with changes in symptoms of depression or anxiety. Furthermore, after return of genetic results, smoking cessation attempts increased (P = 0.003).Conclusion:Even in an underserved population at high risk for adverse psychological reactions, subjects responded positively to personalized genetic results.Genet Med 17 5, 374–379.

Toward the implementation of genomic applications for smoking cessation and smoking-related diseases

The incorporation of genomic information into routine care settings is a burgeoning area for investigation in behavioral medicine. The past decade has witnessed rapid advancements in knowledge of genetic biomarkers associated with smoking behaviors and tobacco-related morbidity and mortality, providing the basis for promising genomic applications in clinical and community settings. We assessed the current state of readiness for implementing genomic applications involving variation in the α5 nicotinic cholinergic receptor subunit gene CHRNA5 and smoking outcomes (behaviors and related diseases) using a process that could be translatable to a wide range of genomic applications in behavioral medicine. We reviewed the scientific literature involving CHRNA5 genetic variation and smoking cessation, and then summarized and synthesized a chain of evidence according to analytic validity, clinical validity, clinical utility, and ethical, legal, and social implications (ACCE), a well-established set of criteria used to evaluate genomic applications. Our review identified at least three specific genomic applications for which implementation may be considered, including the use of CHRNA5 genetic test results for informing disease risk, optimizing smoking cessation treatment, and motivating smoking behavior change. For these genomic applications, we rated analytic validity as convincing, clinical validity as adequate, and clinical utility and ethical, legal, and social implications as inadequate. For clinical genomic applications involving CHRNA5 variation and smoking outcomes, research efforts now need to focus on establishing clinical utility. This approach is compatible with pre-implementation research, which is also needed to accelerate translation, improve innovation design, and understand and refine system processes involved in implementation. This study informs the readiness to incorporate smoking-related genomic applications in real-world settings and facilitates cross-disciplinary collaboration to accelerate the integration of evidence-based genomics in behavioral medicine.

Tobacco Use Prevalence and Smoking Cessation Pharmacotherapy Prescription Patterns Among Hospitalized Patients by Medical Specialty

INTRODUCTION Effective smoking cessation medications are readily available but may be underutilized in hospital settings. In our large, tertiary care hospital, we aimed to (1) characterize patient tobacco use prevalence across medical specialties, (2) determine smoking cessation pharmacotherapy prescription variation across specialties, and (3) identify opportunities for improvement in practice. METHODS Using electronic health records at Barnes Jewish Hospital, we gathered demographic data, admitting service, admission route, length of stay, self-reported tobacco use, and smoking cessation prescriptions over a 6-year period, from 2010 to 2016. We then compared tobacco use prevalence and smoking cessation prescriptions across medical specialties using a cross-sectional, retrospective design. RESULTS Past 12-month tobacco use was reported by patients in 27.9% of inpatient admissions; prescriptions for smoking cessation pharmacotherapy were provided during 21.5% of these hospitalizations. The proportion of patients reporting tobacco use was highest in psychiatry (55.3%) and lowest in orthopedic surgery (17.1%). Psychiatric patients who reported tobacco use were most likely to receive pharmacotherapy (71.8% of admissions), and plastic surgery patients were least likely (4.7% of admissions). Compared with Caucasian tobacco users, African American patients who used tobacco products were less likely to receive smoking cessation medications (adjusted odds ratio [aOR] = 0.65; 95% confidence interval [CI] = 0.62 to 0.68). CONCLUSIONS Among hospitalized tobacco users, safe and cost-effective pharmacotherapies are under-prescribed. We identified substantial variation in prescribing practices across different medical specialties and demographic groups, suggesting the need for an electronic medical record protocol that facilitates consistent tobacco use cessation pharmacotherapy treatment. IMPLICATIONS Tobacco use cessation pharmacotherapy is underutilized during hospitalization, and prescription rates vary greatly across medical specialties and patient characteristics. Hospitals may benefit from implementing policies and practices that standardize and automate the offer of smoking pharmacotherapy for all hospitalized patients who use tobacco.

The significant impact of education, poverty, and race on Internet-based research participant engagement

Purpose:Internet-based technologies are increasingly being used for research studies. However, it is not known whether Internet-based approaches will effectively engage participants from diverse racial and socioeconomic backgrounds.Methods:A total of 967 participants were recruited and offered genetic ancestry results. We evaluated viewing Internet-based genetic ancestry results among participants who expressed high interest in obtaining the results.Results:Of the participants, 64% stated that they were very or extremely interested in their genetic ancestry results. Among interested participants, individuals with a high school diploma (n = 473) viewed their results 19% of the time relative to 4% of the 145 participants without a diploma (P < 0.0001). Similarly, 22% of participants with household income above the federal poverty level (n = 286) viewed their results relative to 10% of the 314 participants living below the federal poverty level (P < 0.0001). Among interested participants both with a high school degree and living above the poverty level, self-identified Caucasians were more likely to view results than self-identified African Americans (P < 0.0001), and females were more likely to view results than males (P = 0.0007).Conclusion:In an underserved population, engagement in Internet-based research was low despite high reported interest. This suggests that explicit strategies should be developed to increase diversity in Internet-based research.Genet Med 19 2, 240–243.

E-cigarette Usage Is Associated With Increased Past-12-Month Quit Attempts and Successful Smoking Cessation in Two US Population–Based Surveys

Introduction We examined past-12-month quit attempts and smoking cessation from 2006 to 2016 while accounting for demographic shifts in the US population. In addition, we sought to understand whether the current use of electronic cigarettes was associated with a change in past-12-month quit attempts and successful smoking cessation at the population level. Methods We analyzed data from 25- to 44-year-olds from the National Health Interview Survey (NHIS) from 2006 to 2016 (N = 26,354) and the Tobacco Use Supplement to the Current Population Survey (TUS-CPS) in 2006-2007, 2010-2011, and 2014-2015 (N = 33,627). Data on e-cigarette use were available in the 2014-2016 NHIS and 2014-2015 TUS-CPS surveys. Results Past-12-month quit attempts and smoking cessation increased in recent years compared with 2006. Current e-cigarette use was associated with higher quit attempts (adjusted odds ratio [aOR] = 2.29, 95% confidence interval [CI] = 1.87 to 2.81, p < .001) and greater smoking cessation (aOR = 1.64, 95% CI = 1.21 to 2.21, p = .001) in the NHIS. Multivariable logistic regression of the TUS-CPS data showed that current e-cigarette use was similarly significantly associated with increased past-12-month quit attempts and smoking cessation. Significant interactions were found for smoking frequency (everyday and some-day smoking) and current e-cigarette use for both outcomes (p < .0001) with the strongest positive effects seen in everyday smokers. Conclusions Compared with 2006, past-12-month quit attempts and smoking cessation increased among adults aged 25-44 in recent years. Current e-cigarette use was associated with increased past-12-month quit attempts and successful smoking cessation among established smokers. These findings are relevant to future tobacco policy decisions. Implications E-cigarettes were introduced into the US market over the past decade. During this period, past-12-month quit attempts and smoking cessation have increased among US adults aged 25-44. These trends are inconsistent with the hypothesis that e-cigarette use is delaying quit attempts and leading to decreased smoking cessation. In contrast, current e-cigarette use was associated with significantly higher past-12-month quit attempts and past-12-month cessation. These findings suggest that e-cigarette use contributes to a reduction in combustible cigarette use among established smokers.

Components Of Alcohol Use And All-Cause Mortality

Importance Current recommendations for low-risk drinking are based on drinking quantity: up to one drink daily for women and two drinks daily for men. Drinking frequency has not been independently examined for its contribution to mortality. Objective To evaluate the impact of drinking frequency on all-cause mortality after adjusting for drinks per day and binge drinking behavior. Design Two independent observational studies with self-reported alcohol use and subsequent all-cause mortality: the National Health Interview Survey (NHIS), and data from Veteran’s Health Administration clinics (VA). Setting Epidemiological sample (NHIS) and VA outpatient database (VA Corporate Data Warehouse). Participants 208,661 individuals from the NHIS interviewed between 1997 and 2009 at the age of 30 to 70 with mortality follow-up in the last quarter of 2011; 75,515 VA outpatients born between 1948 and 1968 who completed an alcohol survey in 2008 with mortality follow-up in June 2016. Exposures Quantity of alcohol use when not binging (1-2 drinks on typical day, 3-4 drinks on typical day), frequency of non-binge drinking (never, weekly or less, 2-3 times weekly, 4 or more times weekly), and frequency of binge drinking (never, less than weekly, 1-3 times weekly, 4 or more times weekly). Covariates included age, sex, race, and comorbidity. Main Outcomes and Measures All-cause mortality. Results After adjusting for binge drinking behavior, survival analysis showed an increased risk for all-cause mortality among people who typically drink 1-2 drinks four or more times weekly, relative to people who typically drink 1-2 drinks at a time weekly or less (NHIS dataset HR=1.15, 95% CI 1.06-1.26; VA dataset HR=1.31, 95% CI 1.15-1.49). Conclusions and Relevance Drinking four or more times weekly increased risk of all-cause mortality, even among those who drank only 1 or 2 drinks daily. This was seen in both a large epidemiological database and a large hospital-based database, suggesting that the results can be generalized.