Association of mitochondrial genome variants with Alzheimer's disease in a Chinese population
Association of mitochondrial genome variants with Alzheimer's disease in a Chinese population
【Abstract】
【Background】
Research on the mitochondrial genome variants of Alzheimer's disease (AD) in Chinese populations is lacking.
【Objective】
The study aimed to identify mitochondrial DNA (mtDNA) variants associated with AD risk and explore therelationship between mtDNA variants and plasma biomarkers in AD patients
【Methods】
Whole genome sequencing was performed in I509 AD patients and 2010 controls from the Chinese popu-lation. mtDNA variants were called according to GATK's best practice mitochondrial pipeline. We evaluated the associ-ation of AD risk with mtDNA variants and mitochondrial haplogroup. Common variant (MAF>0.01) based associationanalysis and gene-based tests of rare variants (MAF<0.01) were carried out with PLINK 1.9 and SKAT-O, respectivelySpearman correlation analysis was performed to assess the association between the burden of mtDNA variants andplasma biomarker levels.
【Results】
The frequency of mitochondrial haplogroup G in AD group was nominally higher than control group (p= 0.019OR = I.48). Rare variants of MTCYB gene were significantly enriched in controls compared to AD patients (p=2.8I X10-, OR = 0.886). Besides, the control group exhibited considerably lower mRNA expression of MT-CYB in brain regionscompared to AD patients in GEO database. Furthermore, the number of mtDNA indel variants per individual correlatedpositively with plasma AB42 levels
【Conclusions】
Mitochondrial haplogroup G may serve as a risk factor for AD, while rare variants of MT-CYB gene acted asprotective factor against AD in mainland China. Moreover, mtDNA variants were related to AD plasma biomarker levels.Our findings highlighted the role of mitochondrial genome variants in the pathogenesis of AD.