{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lee S"],"funding":["Cure Alzheimer's Fund","NIMH NIH HHS","Cure Alzheimer&apos;s Fund","National Institutes of Health","NIH HHS"],"pagination":["3397-3405"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11095441"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(5)"],"pubmed_abstract":["<h4>Introduction</h4>Genome-wide association studies have identified numerous disease susceptibility loci (DSLs) for Alzheimer's disease (AD). However, only a limited number of studies have investigated the dependence of the genetic effect size of established DSLs on genetic ancestry.<h4>Methods</h4>We utilized the whole genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP) including 35,569 participants. A total of 25,459 subjects in four distinct populations (African ancestry, non-Hispanic White, admixed Hispanic, and Asian) were analyzed.<h4>Results</h4>We found that nine DSLs showed significant heterogeneity across populations. Single nucleotide polymorphism (SNP) rs2075650 in translocase of outer mitochondrial membrane 40 (TOMM40) showed the largest heterogeneity (Cochran's Q = 0.00, I<sup>2</sup> = 90.08), followed by other SNPs in apolipoprotein C1 (APOC1) and apolipoprotein E (APOE). Two additional loci, signal-induced proliferation-associated 1 like 2 (SIPA1L2) and solute carrier 24 member 4 (SLC24A4), showed significant heterogeneity across populations.<h4>Discussion</h4>We observed substantial heterogeneity for the APOE-harboring 19q13.32 region with TOMM40/APOE/APOC1 genes. The largest risk effect was seen among African Americans, while Asians showed a surprisingly small risk effect."],"journal":["Alzheimer's & dementia : the journal of the Alzheimer's Association"],"pubmed_title":["On the effect heterogeneity of established disease susceptibility loci for Alzheimer's disease across different genetic ancestries."],"pmcid":["PMC11095441"],"funding_grant_id":["R01MH129337","R01 MH129337"],"pubmed_authors":["Alzheimer's Disease Neuroimaging Initiative (ADNI)","Lutz SM","Lee S","Hecker J","Hahn G","Prokopenko D","Lange C","Tanzi RE","Mullin K"],"additional_accession":[]},"is_claimable":false,"name":"On the effect heterogeneity of established disease susceptibility loci for Alzheimer's disease across different genetic ancestries.","description":"<h4>Introduction</h4>Genome-wide association studies have identified numerous disease susceptibility loci (DSLs) for Alzheimer's disease (AD). However, only a limited number of studies have investigated the dependence of the genetic effect size of established DSLs on genetic ancestry.<h4>Methods</h4>We utilized the whole genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP) including 35,569 participants. A total of 25,459 subjects in four distinct populations (African ancestry, non-Hispanic White, admixed Hispanic, and Asian) were analyzed.<h4>Results</h4>We found that nine DSLs showed significant heterogeneity across populations. Single nucleotide polymorphism (SNP) rs2075650 in translocase of outer mitochondrial membrane 40 (TOMM40) showed the largest heterogeneity (Cochran's Q = 0.00, I<sup>2</sup> = 90.08), followed by other SNPs in apolipoprotein C1 (APOC1) and apolipoprotein E (APOE). Two additional loci, signal-induced proliferation-associated 1 like 2 (SIPA1L2) and solute carrier 24 member 4 (SLC24A4), showed significant heterogeneity across populations.<h4>Discussion</h4>We observed substantial heterogeneity for the APOE-harboring 19q13.32 region with TOMM40/APOE/APOC1 genes. The largest risk effect was seen among African Americans, while Asians showed a surprisingly small risk effect.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-03T03:58:38.165Z","creation":"2026-04-24T03:09:48.241Z"},"accession":"S-EPMC11095441","cross_references":{"pubmed":["38563508"],"doi":["10.1002/alz.13796"]}}