It took more than a million samples, but researchers have managed to extract seven fresh AD risk loci from a genome-wide association study. Published September 7 in Nature Genetics, this GWAS included 90,338 samples from people who were either diagnosed with AD or had a family history of the disease, as well as from 1,036,225 controls. It pegged 38 AD risk loci, 31 of which had been netted in previous GWAS. Seven new ones included two that had been previously tied to frontotemporal dementia, and five relative newcomers to neurodegeneration. In all, the findings build further support for the role of microglia, immune function, and protein homeostasis in AD.
- From more than 90,000 cases and a million controls, a GWAS pulled 38 AD risk loci.
- Among seven new ones, TMEM106B and GRN were previously tied to frontotemporal dementia.
- Variants implicate immunity and protein catabolism in Alzheimer’s disease.
Despite eclipsing the million-person milestone, this latest GWAS, led by Danielle Posthuma of VU Amsterdam, The Netherlands, identified fewer risk loci than a recently posted study led by Jean-Charles Lambert at the Institut Pasteur de Lille in France, which identified 75 loci, including 42 new ones, from 111,326 cases and 677,663 controls (Feb 2021 news). First author Douglas Wightman attributed the bigger haul of Lambert’s GWAS both to the larger number of cases included in that study and to the authors’ generation of novel genotyping data.
For their study, Wightman and colleagues drew genotyping data from 13 cohorts, including the International Genomics of Alzheimer’s Project (IGAP), deCODE, UK Biobank, 23andMe, BioVU, the Trøndelag Health Study, DemGene, TwinGene, STSA, GR@CE, Gothenburg, ANMerge, and Finngen. The 90,338 cases included 43,725 AD and 46,613 proxy cases, i.e., people with a family history of AD. Of the 1,036,225 controls, 318,246 were considered proxy controls, having no family history of AD. The study more than doubles the sample size of a previous GWAS led by many of the same authors, adding more than 18,000 cases and 650,000 controls (Mar 2019 news on Jansen et al., 2019).
Read the full article on the Alz Forum website – https://www.alzforum.org/news/research-news/million-samples-gwas-squeezes-out-seven-new-alzheimers-spots