1.
Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.
Jones, G, Trajanoska, K, Santanasto, AJ, Stringa, N, Kuo, CL, Atkins, JL, Lewis, JR, Duong, T, Hong, S, Biggs, ML, et al
Nature communications. 2021;(1):654
Abstract
Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10-17), arthritis (GDF5 p = 4 × 10-13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.
2.
The association between the methionine/valine (M/V) polymorphism (rs1799990) in the PRNP gene and the risk of Alzheimer disease: an update by meta-analysis.
He, J, Li, X, Yang, J, Huang, J, Fu, X, Zhang, Y, Fan, H
Journal of the neurological sciences. 2013;(1-2):89-95
Abstract
BACKGROUND The M/V polymorphism in the PRNP gene has been extensively examined for the association to the risk of Alzheimer disease (AD); however, results from different studies have been inconsistent. The aim of this study is to evaluate the association between the M/V polymorphism in the PRNP gene and the risk of AD. METHODS A meta-analysis was carried out to analyze the association between the M/V polymorphism in the PRNP gene and the risk of AD. RESULTS A total of 4228 cases and 4324 controls in 16 case-control studies were included in the meta-analysis. The results indicated that the variant V allele carriers (VV+MV) had a 13% decreased risk of AD, when compared with the homozygote MM (VV+MV vs. MM: OR=0.87, 95% CI=0.79-0.96, P=0.004). In the subgroup analysis by ethnicity, significant decreased risks of AD were found in the Caucasian V allele carriers (OR=0.85, 95% CI=0.77-0.94, P=0.002), but not in Asian V allele carriers (OR=1.11, 95% CI=0.78-1.57, P=0.57). In the subgroup analysis by age of onset, significant decreased risks of AD were associated with V allele carriers in late-onset Alzheimer disease (OR=0.76, 95% CI=0.62-0.93, P=0.007) but not in early-onset Alzheimer disease (OR=0.86, 95% CI=0.70-1.06, P=0.17). CONCLUSIONS Our results suggest that the M/V polymorphism in the PRNP gene contributes to the susceptibility of Alzheimer disease.