Alzheimer’s disease (AD) is a common, relentlessly progressive neurodegenerative condition. Late-onset AD has a strong genetic component, with an estimated heritability of around 75%. Over 20 genetic loci have been identified as associated with AD in genome-wide association studies (GWAS), though additional genetic variants also contribute to AD development. Polygenic scores (PGS) are derived from summary statistics from a and aggregate the effects of many disease-associated loci. Other analyses using GWAS data have explored disease-pathways implicated in AD. These have highlighted several areas of biology, notably immune response and cholesterol metabolism disease pathways. More recent studies have combined PGS and disease-pathway approaches by looking at disease pathway-specific PGS. These can be used to explore how genetic risk in disease pathways manifests. Studying these manifestations can greatly increase our understanding of AD disease pathways, and could allow us to stratify patients by disease activity in different areas of biology.
In this systematic we analysed studies examining associations between PGS in AD and various phenotypic outcomes.
We searched the literature using EMBASE, Medline and PsychINFO (from January 2009- August 2018) following PRISMA guidelines. We defined our search terms at the outset. We also hand-searched the reference lists of relevant articles. Each study was assessed for inclusion by two independent researchers. Study inclusion was based on predetermined criteria and data was extracted independently and in duplicate.
Results & Discussion
Our initial search yielded 4717 articles. 3275 articles remained after duplicates were removed. After reading titles and abstracts, 3307 articles were discarded leaving 88 full texts for assessment. The results will be presented and discussed.