biostudies-literatureNazarian ANIA NIH HHS3147-3161https://www.ebi.ac.uk/biostudies/studies/S-EPMC12181559biostudies-literatureUnknown47(3)Genetics is the second strongest risk factor for Alzheimer's disease (AD) after age. More than 70 loci have been implicated in AD susceptibility so far, and the genetic architecture of AD entails both additive and nonadditive contributions from these loci. To better understand nonadditive impact of single-nucleotide polymorphisms (SNPs) on AD risk, we examined individual, joint, and interacting (SNPxSNP) effects of 139 and 66 SNPs mapped to the BIN1 and MS4A6A AD-associated loci, respectively. The analyses were conducted by fitting three respective dominant allelic-effect models using data from four independent studies. Joint effects were analyzed by considering pairwise combinations of genotypes of the selected SNPs, i.e., compound genotypes (CompG). The individual SNP analyses showed assGeroScienceComplex genetic interactions affect susceptibility to Alzheimer's disease risk in the BIN1 and MS4A6A loci.PMC12181559R01AG070488R01 AG061853R01AG061853R01 AG070488R01 AG065477R01AG065477Kulminski AMMorado MNazarian AfalseComplex genetic interactions affect susceptibility to Alzheimer's disease risk in the BIN1 and MS4A6A loci.Genetics is the second strongest risk factor for Alzheimer's disease (AD) after age. More than 70 loci have been implicated in AD susceptibility so far, and the genetic architecture of AD entails both additive and nonadditive contributions from these loci. To better understand nonadditive impact of single-nucleotide polymorphisms (SNPs) on AD risk, we examined individual, joint, and interacting (SNPxSNP) effects of 139 and 66 SNPs mapped to the BIN1 and MS4A6A AD-associated loci, respectively. The analyses were conducted by fitting three respective dominant allelic-effect models using data from four independent studies. Joint effects were analyzed by considering pairwise combinations of genotypes of the selected SNPs, i.e., compound genotypes (CompG). The individual SNP analyses showed ass2025-01-01T00:00:00Z2025 Jun2026-06-02T22:40:08.721Z2026-04-21T03:14:26.936ZS-EPMC121815593975171510.1007/s11357-024-01477-6