While genome-wide association studies (GWAS) of well-defined diseases and disorders such as diabetes and cardiovascular disorders, have successfully identified biological pathways leading to novel understanding and in some cases novel treatments, the genetics behind more complex, neurological & psychiatric disorders remain poorly understood. Part of the problem may lie in the fact that clinical characterization of diseases and disorders affecting the central nervous system (CNS) continue to evolve as witnessed by changes in diagnostic classification systems such as the DSM. Genetic studies of CNS disorders may thus be limited by historical phenotype classifications that perhaps blur lines between truly related biological disease categories.
The proposed research will perform GWAS analyses of multiple relevant CNS phenotypes defined from the UK Biobank´s datasets. In over 20 years of CNS study at deCODE genetics we have run GWAS on a wide range of CNS phenotypes based on, a) diagnostic data (Alzheimer’s, Parkinson’s, Schizophrenia, Bipolar Disorder, Depression, Anxiety, Autism, Migraine, and Chronic Pain disorders, to name a few), b) various measures of cognitive functioning, and c) brain-imaging data (structural and functional MRI). Using methods such as clustering and principal component analyses, we have defined novel CNS phenotypes that we aim to test in UK Biobank data for replication and for increased discovery power in meta-analyses with Icelandic data. Genetic analyses will incorporate multivariate genome-wide complex trait analyses and polygenic prediction of the relationships identified. Additionally we aim to investigate the pleiotropy of variants currently known to associate with CNS phenotypes, thereby contributing new knowledge on the genetic sharing between CNS diseases, brain structure, and normal and abnormal cognitive function and their relationship to environmental and lifestyle-related health outcomes.
