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

BackgroundAlthough the molecular basis of Alzheimer's disease (AD) is often studied in Caucasians, its genetic basis in Bangladesh remains elusive.ObjectiveWe explored the association between single-nucleotide variants (SNVs) of Apolipoprotein E (<i>APOE</i>) and other genes for AD risk among Bangladeshis.MethodsWe 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.ResultsA 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 <i>APOE</i> 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 <i>APOE</i> variant rs429358 with a -logP value of 3, followed by <i>BDNF</i> gene variant rs6265 at 1.3, and <i>CR1</i> gene variant rs1349409945 at 1.2.ConclusionsThe <i>APOE</i> variant rs429358 is linked to an 8-fold increased risk of AD among Bangladeshis.