Faculty Bibliography

Two renal-risk variants in the apolipoprotein L1 gene (APOL1) in African American (AA) deceased donors (DD) are associated with shorter renal allograft survival after transplantation. To identify additional genes contributing to allograft survival, a genome-wide association study was performed in 532 AA DDs. Phenotypic data were obtained from the Scientific Registry of Transplant Recipients. Association and single nucleotide polymorphism (SNP)-by-APOL1 interaction tests were conducted using death-censored renal allograft survival accounting for relevant covariates. Replication and inverse-variance weighted meta-analysis were performed using data from 250 AA DD in the Genomics of Transplantation study. Accounting for APOL1, multiple SNPs near the Nudix Hydrolase 7 gene (NUDT7) showed strong independent effects (p=1.6x10^-8 -2.2x10^-8 ). Several SNPs in the Translocation protein SEC63 homolog (SEC63; p=2x10^-9 -3.7x10^-8 ) and plasmacytoma variant translocation 1 (PVT1) genes (p=4.0x10^-8 -7x10^-8 ) modified the effect of APOL1 on allograft survival. SEC63 is expressed in human renal tubule cells and glomeruli and PVT1 is associated with diabetic kidney disease. Overall, associations were detected for 41 SNPs (p=2x10^-9 -5x10^-8 ) contributing independently or interacting with APOL1 to impact renal allograft survival after transplantation from AA DD. Given the small sample size of the discovery and replication sets, independent validations and functional genomic efforts are needed to validate these results.

BACKGROUND:Unhealthy alcohol use is a leading cause of morbidity and mortality among young people, including university students. Delivering secondary prevention interventions against unhealthy alcohol use is challenging. Information technology has the potential to reach large parts of the general population. The present study is proposed to test a proactive secondary prevention smartphone-based intervention against unhealthy alcohol use. METHODS:This is a parallel-group, randomized controlled trial (1:1 allocation ratio) among 1696 university students with unhealthy alcohol use, identified by screening and followed up at 3, 6, and 12 months. Participants will be randomized to receive access to a smartphone-based intervention or to a no intervention control condition. The primary outcome will be self-reported volume of alcohol drunk over the past 30 days, reported as the mean number of standard drinks per week over the past 30 days, measured at 6 months. Secondary outcomes will be number of heavy drinking days over the past 30 days, at 6 months. Additional outcomes will be maximum number of drinks on any day over the past 30 days, alcohol-related consequences (measured using the Short Inventory of Problems (SIP-2R), and academic performance. DISCUSSION/CONCLUSIONS:The aim of this trial is to close the evidence gap on the efficacy of smartphone-based secondary prevention interventions. If proven effective, smartphone-based interventions have the potential to reach a large portion of the population, completing what is available on the Internet. TRIAL REGISTRATION/BACKGROUND:ISRCTN, 10007691. Registered on 2 December 2019. Recruitment will start in April 2020.

Diabetes is one of the most common chronic diseases among persons aged <20 years (1). Onset of diabetes in childhood and adolescence is associated with numerous complications, including diabetic kidney disease, retinopathy, and peripheral neuropathy, and has a substantial impact on public health resources (2,3). From 2002 to 2012, type 1 and type 2 diabetes incidence increased 1.4% and 7.1%, respectively, among U.S. youths (4). To assess recent trends in incidence of diabetes in youths (defined for this report as persons aged <20 years), researchers analyzed 2002-2015 data from the SEARCH for Diabetes in Youth Study (SEARCH), a U.S. population-based registry study with clinical sites located in five states. The incidence of both type 1 and type 2 diabetes in U.S. youths continued to rise at constant rates throughout this period. Among all youths, the incidence of type 1 diabetes increased from 19.5 per 100,000 in 2002-2003 to 22.3 in 2014-2015 (annual percent change [APC] = 1.9%). Among persons aged 10-19 years, type 2 diabetes incidence increased from 9.0 per 100,000 in 2002-2003 to 13.8 in 2014-2015 (APC = 4.8%). For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites. These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.

The trend of e-cigarette use among teens is ever increasing. Here we show the dysbiotic oral microbial ecology in e-cigarette users influencing the local host immune environment compared with non-smoker controls and cigarette smokers. Using 16S rRNA high-throughput sequencing, we evaluated 119 human participants, 40 in each of the three cohorts, and found significantly altered beta-diversity in e-cigarette users (p = 0.006) when compared with never smokers or tobacco cigarette smokers. The abundance of Porphyromonas and Veillonella (p = 0.008) was higher among vapers. Interleukin (IL)-6 and IL-1β were highly elevated in e-cigarette users when compared with non-users. Epithelial cell-exposed e-cigarette aerosols were more susceptible for infection. In vitro infection model of premalignant Leuk-1 and malignant cell lines exposed to e-cigarette aerosol and challenged by Porphyromonas gingivalis and Fusobacterium nucleatum resulted in elevated inflammatory response. Our findings for the first time demonstrate that e-cigarette users are more prone to infection.

PURPOSE/UNASSIGNED:To identify rates and sociodemographic correlates of food insecurity among low-income smokers. DESIGN/UNASSIGNED:Cross-sectional analysis of baseline survey data from a randomized controlled trial (N = 403) testing a smoking cessation intervention for low-income smokers. SETTING/UNASSIGNED:Two safety-net hospitals in New York City. SAMPLE/UNASSIGNED:Current smokers with annual household income <200% of the federal poverty level. MEASURES/UNASSIGNED:Food insecurity was measured using the United States Department of Agriculture 6-item food security module. Participant sociodemographics were assessed by self-reported survey responses. ANALYSIS/UNASSIGNED:We used frequencies to calculate the proportion of smokers experiencing food insecurity and multivariable logistic regression to identify factors associated with being food insecure. RESULTS/UNASSIGNED:Fifty-eight percent of participants were food insecure, with 29% reporting very high food insecurity. Compared to married participants, separated, widowed, or divorced participants were more likely to be food insecure (adjusted odds ratio [AOR] = 2.33, 95% confidence interval [CI]: 1.25-4.33), as were never married participants (AOR = 2.81, 95% CI: 1.54-5.14). CONCLUSIONS/UNASSIGNED:food access) may be needed for low-income populations. Interventions which seek to alleviate food insecurity may benefit from targeting socially isolated smokers.

OBJECTIVE:Electronic dance music (EDM) party attendees are a high-risk population for drug use and associated adverse effects. We examined trends in past-year drug use within this population to better inform prevention and harm reduction efforts. METHODS:Each summer from 2016 through 2019, we used time-space sampling to survey a cross-section of adults entering EDM parties at randomly selected nightclubs and at dance festivals in New York City. Ns ranged from 504 (2019) to 1,087 (2016). We estimated log-linear trends in past-year use of 16 different synthetic drugs or drug classes. RESULTS:Between 2016 and 2019, estimated past-year prevalence of use of ketamine increased from 5.9% to 15.3% (a 157.6% relative increase; P = .007), LSD use increased from 9.9% to 16.6% (a 67.7% relative increase, P < .001), powder cocaine use increased from 17.3% to 35.2% (a 103.5% relative increase, P < .001), and GHB use increased from 1.0% to 4.2% (a 311.8% relative increase; P = .002). Past-year use of >3 drugs increased from 12.7% to 20.5% (a 61.4% relative increase; P = .013); however, estimated past-year use of unknown powders decreased from 2.0% to 1.1% (a relative 44.7% decrease; P = .038) and ecstasy/MDMA/Molly use was stable across years (at 25.0 to 28.5 %; P = .687). CONCLUSIONS:Reports of powder cocaine, LSD, ketamine, and GHB are becoming more prevalent among EDM party attendees. Prevention and harm reduction efforts are needed to address increasing use. Research is also needed to examine whether increasing media coverage of medical use of ketamine and other psychedelics affects prevalence of recreational use.

BACKGROUND:Research exploring the longitudinal course of posttraumatic stress disorder (PTSD) symptoms has documented four modal trajectories (low, remitting, high, and delayed), with proportions varying across studies. Heterogeneity could be due to differences in trauma types and patient demographic characteristics. METHODS:This analysis pooled data from six longitudinal studies of adult survivors of civilian-related injuries admitted to general hospital emergency departments (EDs) in six countries (pooled N = 3083). Each study included at least three assessments of the clinician-administered PTSD scale in the first post-trauma year. Latent class growth analysis determined the proportion of participants exhibiting various PTSD symptom trajectories within and across the datasets. Multinomial logistic regression analyses examined demographic characteristics, type of event leading to the injury, and trauma history as predictors of trajectories differentiated by their initial severity and course. RESULTS:Five trajectories were found across the datasets: Low (64.5%), Remitting (16.9%), Moderate (6.7%), High (6.5%), and Delayed (5.5%). Female gender, non-white race, prior interpersonal trauma, and assaultive injuries were associated with increased risk for initial PTSD reactions. Female gender and assaultive injuries were associated with risk for membership in the Delayed (v. Low) trajectory, and lower education, prior interpersonal trauma, and assaultive injuries with risk for membership in the High (v. Remitting) trajectory. CONCLUSIONS:The results suggest that over 30% of civilian-related injury survivors admitted to EDs experience moderate-to-high levels of PTSD symptoms within the first post-trauma year, with those reporting assaultive violence at increased risk of both immediate and longer-term symptoms.

Mobile technology has created the opportunity for health systems to provide low cost tobacco cessation assistance to patients. The goal of the present study was to examine the feasibility and effectiveness of an intervention (Text2Connect) that uses text messages to offer proactive connection to the New York State Smokers' Quitline. The electronic health record at two urban health systems was queried for patients who were current smokers and who had an outpatient visit between March 2015 and February 2016. Smokers (N = 4000) were sent an informational letter. Those who did not opt out (N = 3719) were randomized to one of 6 message sequences in order to examine the effect of theoretically informed message frames on response rates. Participants were sent a series of text messages at baseline and at 1 month and were asked to reply in order to be contacted by the state quitline (QL). After removing 1403 nonworking numbers, texts were sent to 2316 patients, and 10.0% (205/2060) responded with a QL request. Almost one quarter (23.6%, 486/2060) replied STOP and 66.4% (1369/2060) never responded. QL request rates were significantly higher when response efficacy messages were not used (p < .001). There were no differences by message framing on STOP requests (p > .05). The Text2Connect intervention was well accepted with a minority opting out. A 10% QL response rate is noteworthy given that only 5-7 brief outreach text messages were used. Results indicate that simple self-efficacy-focused messaging is most effective at supporting response rates.

Low-coverage next-generation sequencing experiments assisted by statistical methods are popular in a genetic association study. Next-generation sequencing experiments produce genotype data that include allele read counts and read depths. For low sequencing depths, the genotypes tend to be highly uncertain; therefore, the uncertain genotypes are usually removed or imputed before performing a statistical analysis. It may result in the inflated type I error rate and in a loss of statistical power. In this paper, we propose a mixture-based penalized score association test adjusting for non-genetic covariates. The proposed score test statistic is based on a sandwich variance estimator so that it is robust under the model misspecification between the covariates and the latent genotypes. The proposed method takes advantage of not requiring either external imputation or elimination of uncertain genotypes. The results of our simulation study show that the type I error rates are well controlled and the proposed association test have reasonable statistical power. As an illustration, we apply our statistic to pharmacogenomics data for drug responsiveness among 400 epilepsy patients.