ABSTRACT
OBJECTIVES: Sarcopenia is recognized to be a health problem which is as serious as obesity, but its relevance to mortality is unclear. We conducted a meta-analysis of cohort studies on lean mass and mortality in populations with different health conditions. METHODS: In this study, a systematic search of PubMed, Cochrane Library and Embase was performed for cohort studies published before Dec 20, 2017 which examined the relationship between lean mass and mortality. We included studies reporting lean mass measurement by dual-energy X-ray absorptiometry, bioimpedance analysis or computed tomography, as continuous (per standard deviation [SD] decrease) or binary variables (using sarcopenia cutoffs). We excluded studies which used muscle mass surrogates, anthropometric measurement of muscle, rate of change in muscle mass, and sarcopenia defined by composite criteria. The primary study outcome was all-cause mortality. Pooled hazard ratio estimates were calculated using a random effects model. RESULTS: A total of 9602 articles were identified from the systematic search, and 188 studies with 98 468 participants from 34 countries were included in the meta-analysis. Of the 68 studies included in the present meta-analysis, the pooled HR was 1.36 and 1.74 for every SD decrease in lean mass and in people with low lean mass (cutoffs), respectively. Significant associations were also observed in elderly and all disease subgroups, irrespective of the measurement modalities. CONCLUSIONS: Lower lean mass is robustly associated with increased mortality, regardless of health conditions and lean mass measurement modalities. This meta-analysis highlighted low lean mass as a key public health issue.
ABSTRACT
OBJECTIVE: Thyrotoxic periodic paralysis (TPP) is a rare and potentially fatal complication of hyperthyroidism. By meta-analysis of genome-wide association studies, we aim to discover novel susceptibility loci and understand the pathogenesis of TPP. METHODS: This meta-analysis comprised 319 TPP cases and 3516 healthy controls from three independent cohorts (two from Hong Kong; one from Shanghai). Genetic variants in each cohort were separately genotyped, imputed and analyzed for association with TPP. Fixed-effect meta-analysis was performed to combine the data. Using the three independent genome-wide significant variants, a weighted genetic risk score (GRS) was developed. RESULTS: Of 7 077 246 variants tested for association with TPP, 260 variants reached genome-wide significance and were represented by independent variants from four distinct genomic loci, but a risk locus for Graves' disease at 6p21.33-p21.22 was excluded from subsequent analyses. Two novel loci near TRIM2 (4q31.3; rs6827197: OR = 4.075; P = 3.46 × 10-9) and AC140912.1 (16q22.3; rs6420387: OR = 1.861; P = 2.66 × 10-8) were identified. Together with previously reported KCNJ2 (17q24.3; rs312743: OR = 2.564; P = 1.15 × 10-21), the three susceptibility variants explained 4.36% of the genetic liability. Expression quantitative trait loci analyses showed the variants altered expression of TRIM2 in nerve and KCNJ2 in skeletal muscle. The weighted GRS had an area under curve of 0.827 and 0.682 in the derivation and validation cohorts in Hong Kong. CONCLUSIONS: We identified two novel TPP risk loci near TRIM2 and AC140912.1. While rare mutations in TRIM2 and KCNJ2 were implicated in monogenic disorders characterized by muscle paralysis, our study suggested common variants near these genes might dysregulate gene expression and lead to milder phenotypes.
