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The AUDIT questionnaire is designed to screen for hazardous alcohol use by measuring both alcohol consumption and the problematic consequences of drinking. We performed a genome-wide association study of AUDIT scores in the UK Biobank and the 23andMe cohorts and find several genetic loci that are significantly associated with AUDIT scores. We show that the problem drinking is genetically correlated with psychopathology whereas alcohol consumption shares a genetic profile with a more favourable health profile, i.e. higher HDL cholesterol and lower triglycerides. Our findings show that, while alcohol consumption and problem drinking have overlapping genetic architecture, some of the genes which associate with each trait are distinct. The last 7 questions of the AUDIT questionnaire are important to detect genetic variation which is specific to problem drinking and therefore these items should be retained when attempting to uncover the genetic basis of alcohol use disorders. Finally, we make recommendations about which AUDIT cut-offs to use when trying to create a phenotype that mirrors Alcohol Use Disorders when performing genetic studies.
STratifying Resilience and Depression Longitudinally (STRADL)
Progress in understanding the causes of major depressive disorder has been slow. Dividing depression into subtypes, a process called stratification, could ultimately lead to faster progress. We will stratify or divide individuals with MDD and depressive syndromes into more similar groups of people in UK Biobank. Our aims are to: 1. Identify and describe specific subtypes of depression 2. Identify the causes underlying different types of depression using GWAS and MRI 3. Test whether resistance to depression (i.e. resilience) to depression can be accurately measured. 4. Identify the mechanisms underlying resilience using genetic and brain imaging data. This research seeks to use the medical, cognitive, imaging and genetic data from UKBiobank to study the mechanisms of common medical conditions and use them as a platform to better diagnosis. These aims are consistent with UK Biobank's. Providing this information will help to identify new drug targets for depression. Stratifying depression into more homogenous categories will provide better 'disease' targets for other research studies because there will be less lumping together of individuals with different causes for their illness within the same broad category of depression. We will test whether these sub-classes of depression and depressive symptom have neurobiological associations in UKbiobank by comparing them with depressed individuals as w whole, as well as controls, using MRI and genetic data. We will firstly examine the associations of depression with cognition (baseline measures and web-based measures of attention and memory, for example), brain structure, function and connection strength (MRI). We will examine the association of different depression types with biological intermediates (measurable variables important in the causation of depression) using a technique called polygenic profiling. We will also compare resilient and non-resilient individuals. We are interested in the full UKbiobank cohort for most analyses - and the subgroup of UKbiobank with genetic and imaging (brain MRI) data for more detailed analysis.