Gender-Specific Next-Generation Sequencing Reveals First Allelic Variation Patterns in Dementia Risk Among Bangladeshis: The CARED Study
Year: 2025
Type: article
Abstract: Redoy Ranjan,1,2 Md Abdullah Yusuf,3 Mohammad Nur Uddin,4 Mim Tanzila Mamun,5 Alif Al Mamun,6,7 Ghulam Kawnayn,8 Maliha Hakim4 1Department of Biological Sciences, Royal Holloway University of London, London, UK; 2Department of Cardiac Surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 3Department of Microbiology, National Institute of Neurosciences and Hospital, Dhaka, Bangladesh; 4Department of Neurology, National Institute of Neurosciences and Hospital, Dhaka, Bangladesh; 5Department of Medicine, Chottogram Army Medical College, Chottogram, Bangladesh; 6Department of Neuroscience, Macquarie University, Sydney, NSW, Australia; 7Department of Education, Southern Cross University, Sydney, Australia; 8Department of Neurology, Combined Military Hospital, Chottogram, BangladeshCorrespondence: Maliha Hakim, Department of Neurology, National Institute of Neurosciences and Hospital, Dhaka, Bangladesh, Email [email protected]: Alzheimer’s disease (AD) and related dementias exhibit significant gender disparities in prevalence and progression, yet the genetic underpinnings of these differences remain incompletely understood. We aimed to observe gender-specific allelic variation patterns in key dementia susceptibility genes among the Bangladeshi population.Methods: The Community Awareness and Research on Early Dementia (CARED) study is a case-control study that recruited age- and gender-adjusted AD patients and healthy controls aged ≥ 18 years between 2022 and 2024. We conducted a next-generation sequencing (NGS) analysis of 112 individuals (57 males and 55 females), focusing on key genes associated with dementia susceptibility. Chi-square tests were used to assess gender-specific allele frequency differences for each variant. While Bonferroni-corrected thresholds are noted for reference, nominal P-values are reported due to the study’s exploratory design and limited sample size.Results: The NGS analysis of dementia-associated variants found distinct genotype distribution patterns for Apolipoprotein E (APOE) (rs429358, rs7412, and rs405509), Brain-Derived Neurotrophic Factor (BDNF) (rs6265), and Catechol-O-methyltransferase (COMT) (rs4680) in males and females. We observed a higher minor allele frequency (MAF) of APOE rs429358 in females than males (23.7% vs 15.8%), while APOE rs405509 showed a stronger effect in males, with a significantly higher homozygous MAF (17.5% vs 5.5%, P = 0.05). The BDNF variant rs6265 also showed a greater prevalence in males, with a higher proportion of homozygous carriers (10.7% vs 3.8%) than in females. Linkage disequilibrium (LD) analysis revealed a strong association between APOE rs429358 and rs7412 (r² =0.85), with a rapid decay in LD beyond 10 kb (mean r² =0.15) in the APOE region.Conclusion: We identified APOE rs405509 and BDNF rs6265 as potential genetic variants associated with gender-specific susceptibility to dementia among Bangladeshis. Additionally, APOE variants rs429358 and rs7412 exhibited strong linkage disequilibrium, with rapid decay from the APOE locus, indicating a higher rate of genetic mixing in this population. Given the exploratory nature of this study, large-scale validation is warranted to confirm these findings.Keywords: next-generation sequencing, dementia, gender differences, APOE, genetic variants
Authors: Ranjan R, Yusuf MA, Uddin MN, Mamun MT, Mamun AA, Kawnayn G, Hakim M
Institution: Neurology, Inc
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7087864292
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