Genomic analyses reveal new insights into Alzheimer’s disease
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Alzheimer’s disease (AD) is the most common cause of dementia, with global case numbers projected to reach 153 million in 2050 1 . AD is highly heritable, with twin-based heritability estimates of 60-80% 2 . While 1,200 causal loci are predicted to exist for AD 3 , approximately 80 have been associated with AD in two recent studies 4,5 , suggesting that many loci remain to be discovered 6 . Here, we analyzed data from 183,620 AD cases and 2.6 million controls from diverse ancestries, identifying 118 loci in a multi-ancestry analysis and 9 additional loci in ancestry-specific analyses, 48 of which are new. We identified new AD risk genes, prioritized potential drug targets, and identified microglia and, for the first time, several neuronal cell types enriched for AD-associated genetic risk. Moreover, we improved polygenic prediction and estimated a single-nucleotide polymorphism (SNP) heritability of 19%. Together, our findings offer insights into the genetic architecture and potential pathobiology of AD, as well as specific targets for future drug development research.
