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Kunkle BW, Schmidt M, Klein HU, Naj AC, Hamilton-Nelson KL, Larson EB, Evans DA, De Jager PL, Crane PK, Buxbaum JD, Ertekin-Taner N, Barnes LL, Fallin MD, Manly JJ, Go RC, Obisesan TO, Kamboh MI, Bennett DA, Hall KS, Goate AM, Foroud TM, Martin ER, Wang LS, Byrd GS, Farrer LA, Haines JL, Schellenberg GD, Mayeux R, Pericak-Vance MA, Reitz C, Writing Group for the Alzheimer’s Disease Genetics Consortium (ADGC), Graff-Radford NR, Martinez I, Ayodele T, Logue MW, Cantwell LB, Jean-Francois M, Kuzma AB, Adams LD, Vance JM, Cuccaro ML, Chung J, Mez J, Lunetta KL, Jun GR, Lopez OL, Hendrie HC, Reiman EM, Kowall NW, Leverenz JB, Small SA, Levey AI, Golde TE, Saykin AJ, Starks TD, Albert MS, Hyman BT, Petersen RC, Sano M, Wisniewski T, Vassar R, Kaye JA, Henderson VW, DeCarli C, LaFerla FM, Brewer JB, Miller BL, Swerdlow RH, Van Eldik LJ, Paulson HL, Trojanowski JQ, Chui HC, Rosenberg RN, Craft S, Grabowski TJ, Asthana S, Morris JC, Strittmatter SM, Kukull WA. Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel: A Meta-analysis. JAMA Neurol. 2021 Jan 1;78(1):102-113. PubMed.
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Washington University School of Medicine
This is a very nice study. It is the largest GWAS in African Americans so far, though it is far below the sample size of the genetic studies from Europeans, which included almost 100,000 individuals.
This study suggests that it is possible additional genes can be identified by studying different populations. This will lead to the identification of more genes and networks implicated in AD. If we want to identify all genes involved in Alzheimer’s risk, we need to study different races.
Overall, I do not think this, or the European-focused studies, identifies race-specific genes and pathways. The variants reported here are specific to African Americans, but I think the identified genes will be implicated in disease independently of race.
The results we have so far are just the tip of the iceberg; larger studies will lead to many more hits. Larger studies will also allow more proper comparison of the genetic architecture of AD in African Americans versus non-Hispanic whites.
My only minor concern with this study is that there is not a real replication study. Therefore, additional studies will be instrumental to confirm that the genes identified here are associated with AD in African Americans.
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