**Jedd Pratt 1,2,\*, Colin Boreham 1, Sean Ennis 2,3, Anthony W. Ryan <sup>2</sup> and Giuseppe De Vito 1,4**


Received: 22 November 2019; Accepted: 18 December 2019; Published: 19 December 2019

**Abstract:** The age-related decline in skeletal muscle mass, strength and function known as 'sarcopenia' is associated with multiple adverse health outcomes, including cardiovascular disease, stroke, functional disability and mortality. While skeletal muscle properties are known to be highly heritable, evidence regarding the specific genes underpinning this heritability is currently inconclusive. This review aimed to identify genetic variants known to be associated with muscle phenotypes relevant to sarcopenia. PubMed, Embase and Web of Science were systematically searched (from January 2004 to March 2019) using pre-defined search terms such as "aging", "sarcopenia", "skeletal muscle", "muscle strength" and "genetic association". Candidate gene association studies and genome wide association studies that examined the genetic association with muscle phenotypes in non-institutionalised adults aged ≥50 years were included. Fifty-four studies were included in the final analysis. Twenty-six genes and 88 DNA polymorphisms were analysed across the 54 studies. The *ACTN3*, *ACE* and *VDR* genes were the most frequently studied, although the *IGF1*/*IGFBP3*, *TNF*α, *APOE*, *CNTF*/*R* and *UCP2*/*3* genes were also shown to be significantly associated with muscle phenotypes in two or more studies. Ten DNA polymorphisms (rs154410, rs2228570, rs1800169, rs3093059, rs1800629, rs1815739, rs1799752, rs7412, rs429358 and 192 bp allele) were significantly associated with muscle phenotypes in two or more studies. Through the identification of key gene variants, this review furthers the elucidation of genetic associations with muscle phenotypes associated with sarcopenia.

**Keywords:** genotype; genetic variation; muscle phenotypes; sarcopenia; aging
