Title | Genetic architecture of Alzheimer's disease. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Neuner SM, Tcw J, Goate AM |
Journal | Neurobiol Dis |
Volume | 143 |
Pagination | 104976 |
Date Published | 2020 09 |
ISSN | 1095-953X |
Keywords | Alzheimer Disease, Genetic Predisposition to Disease, Humans |
Abstract | Advances in genetic and genomic technologies over the last thirty years have greatly enhanced our knowledge concerning the genetic architecture of Alzheimer's disease (AD). Several genes including APP, PSEN1, PSEN2, and APOE have been shown to exhibit large effects on disease susceptibility, with the remaining risk loci having much smaller effects on AD risk. Notably, common genetic variants impacting AD are not randomly distributed across the genome. Instead, these variants are enriched within regulatory elements active in human myeloid cells, and to a lesser extent liver cells, implicating these cell and tissue types as critical to disease etiology. Integrative approaches are emerging as highly effective for identifying the specific target genes through which AD risk variants act and will likely yield important insights related to potential therapeutic targets in the coming years. In the future, additional consideration of sex- and ethnicity-specific contributions to risk as well as the contribution of complex gene-gene and gene-environment interactions will likely be necessary to further improve our understanding of AD genetic architecture. |
DOI | 10.1016/j.nbd.2020.104976 |
Pubmed Link | https://www.ncbi.nlm.nih.gov/pubmed/32565066?dopt=Abstract |
page_expo | Internal |
Alternate Journal | Neurobiol Dis |
PubMed ID | 32565066 |
PubMed Central ID | PMC7409822 |
Grant List | U01 AG052411 / AG / NIA NIH HHS / United States RF1 AG058501 / AG / NIA NIH HHS / United States K01 AG062683 / AG / NIA NIH HHS / United States U01 AG058635 / AG / NIA NIH HHS / United States U19 AG032438 / AG / NIA NIH HHS / United States |
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