Next-generation sequencing study identifies the first genes associated with Alzheimer's disease in Bangladeshi population: The CARED study

Abstract

Background

Although the molecular basis of Alzheimer's disease (AD) is often studied in Caucasians, its genetic basis in Bangladesh remains elusive.

Objective

We explored the association between single-nucleotide variants (SNVs) of Apolipoprotein E (APOE) and other genes for AD risk among Bangladeshis.

Methods

We recruited AD patients and controls aged ≥18 years and conducted next generation sequencing (NGS) to analyze ∼30 Mb of the human exome. The NGS targets ∼99% of the Consensus Coding Sequence and RefSeq annotations, along with the complete mitochondrial genome.

Results

A total of 132 (72 AD: 60 control) age- and sex-matched participants were sequenced. The average age of AD was comparable to that of controls (64.5 ± 11.3 versus 63.6 ± 9.8, p = 0.69), and the gender distribution (p = 0.49) was similar between the study groups. Following NGS analysis 23 SNVs from 16 potential genes were identified. The APOE variant rs429358 was associated with a significantly increased age- and sex- adjusted risk of AD (OR) 8.0 (95% CI: 2.3–27.9, p = 0.001) in the additive model, 10.5 (95% CI: 2.8–39.5, p < 0.001) in the dominant model, and 6.9 (95% CI: 1.8–26.9, p = 0.005) in the heterozygous genotype model, as determined using the Bonferroni adjustment method. The top SNV for predicting AD was the APOE variant rs429358 with a -logP value of 3, followed by BDNF gene variant rs6265 at 1.3, and CR1 gene variant rs1349409945 at 1.2.

Conclusions

The APOE variant rs429358 is linked to an 8-fold increased risk of AD among Bangladeshis.