Tehran University of Medical Sciences

Science Communicator Platform

Share By
New Genetic Associations Between Alzheimer's Disease and Its Key Risk Factors Publisher Pubmed



Gholami M ; Ahmadi A A ; Niaki M A A ; Asouri M ; Saeedi S ; Amoli M M ; Larijani B
Authors

Source: Psychogeriatrics Published:2026


Abstract

Introduction: This study aimed to explore shared genetic architectures underlying Alzheimer's disease (AD) and its known risk factors. Methods: Significant common variants between AD and its risk factors were identified using GWAS data. The 1000 Genomes Project genotyping data enabled the detection of linkage disequilibrium (LD) blocks and haplotype structures. Functional impact assessments, protein–protein interaction analyses, pathway mapping and enrichment studies were performed. Results: Sixteen significant variants across nine genes were associated with AD and at least one risk factor (p ≤ 5 × 10−8). Genes APOE, ABCA1 and TOMM40 showed strong associations with AD (adjusted p = 9.75 × 10−9). High-confidence interactions were identified among these genes, as well as APP and LRP1, within the AD pathway. Variant rs429358 (p ≤ 3 × 10−15) on the APOE gene was linked to AD, metabolic syndrome (MetS), diabetes, waist-to-hip ratio (WHR) and ageing. Variant rs2075650 (p ≤ 6 × 10−9) on TOMM40 correlated AD risk with MetS, WHR and body mass index (BMI). Variants rs483082 (p ≤ 2 × 10−32) and rs71352238 (p ≤ 1 × 10−11) on APOC1 and TOMM40 were associated with AD and MetS. Variants rs4420638 (p ≤ 2 × 10−34) and rs1800978 (p ≤ 2 × 10−9) on APOC1 and ABCA genes were associated with AD and WHR. The rs13237518 (p ≤ 5 × 10−11) was associated with AD risk in diabetic patients. Furthermore, the rs4277405 (p ≤ 9 × 10−20) associated AD with cardiovascular disease (CVD). Haplotypic structures were also identified for all these variants (D′ and r2 ≥ 0.8). Discussion: This study identifies genetic variants and LD blocks on APOE, ABCA1, TOMM40 and APOC1 genes shared between AD and its risk factors, revealing common genetic links and potential shared susceptibility pathways. © 2026 Japanese Psychogeriatric Society.
Related Docs
View other Related Docs
1. Genetic Variants and Haplotype Structures of Mirna Host Genes in Cancer and Obesity, Journal of Biomolecular Structure and Dynamics (2023)
2. Identification of Shared Genetic Variants and Haplotypes Associated With Schizophrenia and Depression, Brain and Behavior (2026)
3. Fto Is a Major Genetic Link Between Breast Cancer, Obesity, and Diabetes, Breast Cancer Research and Treatment (2024)
Experts (# of related papers)
View all Related Experts
Bagher Larijani (3)
Mahsa Mohamad Amoli (2)
Other Related Docs
4. Precision Medicine in Endocrinology Practice, Precision Medicine in Clinical Practice (2022)
5. Identifying the Potential Mediators of Pathological Complete Response to Neoadjuvant Chemotherapy Among Tacr1 Gene Polymorphisms: A Study on Breast Cancer Patients, Breast Cancer Research and Treatment (2025)
6. The Interactions Between Dietary Fats Intake and Caveolin 1 Rs 3807992 Polymorphism With Fat Distribution in Overweight and Obese Women: A Cross-Sectional Study, BMC Medical Genomics (2021)
7. Novel Genetic Association Between Obesity, Colorectal Cancer, and Inflammatory Bowel Disease, Journal of Diabetes and Metabolic Disorders (2023)
8. Dna- and Aptamer-Based Biosensors for Alzheimer's Disease Biomarkers Toward Clinical Translation, Talanta (2027)
9. Haplotypic Variants of Covid-19 Related Genes Are Associated With Blood Pressure and Metabolites Levels, Journal of Medical Virology (2023)
10. Genetic Variants and Haplotype Structures in the Casc Gene Family to Predict Cancer Risk: A Bioinformatics Study, Health Science Reports (2024)
11. An in Silico Approach to Identify and Prioritize Mirnas Target Sites Polymorphisms in Colorectal Cancer and Obesity, Cancer Medicine (2020)
12. Mediation Role of Body Fat Distribution (Fd) on the Relationship Between Cav1 Rs3807992 Polymorphism and Metabolic Syndrome in Overweight and Obese Women, BMC Medical Genomics (2021)