Notes
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. 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 performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112,117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 13 loci. These include SNPs in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and 2 loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, CADM2 and FAM69C.
T K Clarke, et al. Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N =112 117). Molecular Psychiatry (2017) 22, 1376 1384 doi:10.1038/mp.2017.153
Application 4844
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.
We appreciate the time scale for the availability of genotyping and imaging data.
Lead investigator: | Professor Andrew McIntosh |
Lead institution: | University of Edinburgh |