Am J Hum Genet 2020 06 14;106(6):885-892. Epub 2020 May 14.
Medical Research Council (MRC) Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom. Electronic address:
Leveraging high-dimensional molecular datasets can help us develop mechanistic insight into associations between genetic variants and complex traits. In this study, we integrated human proteome data derived from brain tissue to evaluate whether targeted proteins putatively mediate the effects of genetic variants on seven neurological phenotypes (Alzheimer disease, amyotrophic lateral sclerosis, depression, insomnia, intelligence, neuroticism, and schizophrenia). Applying the principles of Mendelian randomization (MR) systematically across the genome highlighted 43 effects between genetically predicted proteins derived from the dorsolateral prefrontal cortex and these outcomes. Read More