Biology subjects

Hartz, S.

Publications and source records attributed to Hartz, S..

3 recordsLinked to original sources

bioRxiv2017

Genome-wide analysis of risk-taking behaviour and cross-disorder genetic correlations in 116,255 individuals from the UK Biobank cohort

Risk-taking behaviour is a key component of several psychiatric disorders and could influence lifestyle choices such as smoking, alcohol use and diet. As a phenotype, risk-taking behaviour therefore fits within a Research Domain Criteria (RDoC) approach, whereby identifying genetic determinants of this trait has the potential to improve our understanding across different psychiatric disorders. Here we report a genome wide association study in 116 255 UK Biobank participants who responded yes/no to the question \"Would you consider yourself a risk-taker?\" Risk-takers (compared to controls) were more likely to be men, smokers and have a history of psychiatric disorder. Genetic loci associated with risk-taking behaviour were identified on chromosomes 3 (rs13084531) and 6 (rs9379971). The effects of both lead SNPs were comparable between men and women. The chromosome 3 locus highlights CADM2, previously implicated in cognitive and executive functions, but the chromosome 6 locus is challenging to interpret due to the complexity of the HLA region. Risk-taking behaviour shared significant genetic risk with schizophrenia, bipolar disorder, attention deficit hyperactivity disorder and post-traumatic stress disorder, as well as with smoking and total obesity. Despite being based on only a single question, this study furthers our understanding of the biology of risk-taking behaviour, a trait which has a major impact on a range of common physical and mental health disorders.

genetics↗

bioRxiv2017

Components Of Alcohol Use And All-Cause Mortality

ImportanceCurrent 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.\n\nObjectiveTo evaluate the impact of drinking frequency on all-cause mortality after adjusting for drinks per day and binge drinking behavior.\n\nDesignTwo independent observational studies with self-reported alcohol use and subsequent all-cause mortality: the National Health Interview Survey (NHIS), and data from Veterans Health Administration clinics (VA).\n\nSettingEpidemiological sample (NHIS) and VA outpatient database (VA Corporate Data Warehouse).\n\nParticipants208,661 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.\n\nExposuresQuantity 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.\n\nMain Outcomes and MeasuresAll-cause mortality.\n\nResultsAfter 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).\n\nConclusions and RelevanceDrinking 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.

epidemiology↗

bioRxiv2017

Association Between Substance Use Disorder And Polygenic Liability To Schizophrenia

BackgroundThere are high levels of comorbidity between schizophrenia and substance use disorder, but little is known about the genetic etiology of this comorbidity.\n\nMethodsHere, we test the hypothesis that shared genetic liability contributes to the high rates of comorbidity between schizophrenia and substance use disorder. To do this, polygenic risk scores for schizophrenia derived from a large meta-analysis by the Psychiatric Genomics Consortium were computed in three substance use disorder datasets: COGEND (ascertained for nicotine dependence n=918 cases, 988 controls), COGA (ascertained for alcohol dependence n=643 cases, 384 controls), and FSCD (ascertained for cocaine dependence n=210 cases, 317 controls). Phenotypes were harmonized across the three datasets and standardized analyses were performed. Genome-wide genotypes were imputed to 1000 Genomes reference panel.\n\nResultsIn each individual dataset and in the mega-analysis, strong associations were observed between any substance use disorder diagnosis and the polygenic risk score for schizophrenia (mega-analysis pseudo R2 range 0.8%-3.7%, minimum p=4x10-23).\n\nConclusionsThese results suggest that comorbidity between schizophrenia and substance use disorder is partially attributable to shared polygenic liability. This shared liability is most consistent with a general risk for substance use disorder rather than specific risks for individual substance use disorders and adds to increasing evidence of a blurred boundary between schizophrenia and substance use disorder.

genetics↗