A genome-wide association study identifies a locus associated with knee extension strength in older Japanese individuals

• Published in: Communications biology Vol. 7; no. 1; pp. 513 - 9
• Main Authors: Ito, Shuji, Takuwa, Hiroshi, Kakehi, Saori, Someya, Yuki, Kaga, Hideyoshi, Kumahashi, Nobuyuki, Kuwata, Suguru, Wakatsuki, Takuya, Kadowaki, Masaru, Yamamoto, Soichiro, Abe, Takafumi, Takeda, Miwako, Ishikawa, Yuki, Liu, Xiaoxi, Otomo, Nao, Suetsugu, Hiroyuki, Koike, Yoshinao, Hikino, Keiko, Tomizuka, Kohei, Momozawa, Yukihide, Ozaki, Kouichi, Isomura, Minoru, Nabika, Toru, Kaneko, Haruka, Ishijima, Muneaki, Kawamori, Ryuzo, Watada, Hirotaka, Tamura, Yoshifumi, Uchio, Yuji, Ikegawa, Shiro, Terao, Chikashi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 20.05.2024; Nature Publishing Group UK; Nature Portfolio
• Subjects: Aged; Asian People - genetics; Cytoskeleton; East Asian People; Female; Genome-wide association studies; Genome-Wide Association Study; Genomes; Humans; Japan; Knee; Male; Middle Aged; Muscle strength; Muscle Strength - genetics; Muscle, Skeletal - metabolism; Musculoskeletal system; Myotonic dystrophy; Older people; Polymorphism, Single Nucleotide; Sarcopenia; Sarcopenia - genetics; Sarcopenia - physiopathology; Skeletal muscle; Therapeutic targets; Japan
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06108-6

Sarcopenia is a common skeletal muscle disease in older people. Lower limb muscle strength is a good predictive value for sarcopenia; however, little is known about its genetic components. Here, we conducted a genome-wide association study (GWAS) for knee extension strength in a total of 3452 Japanese aged 60 years or older from two independent cohorts. We identified a significant locus, rs10749438 which is an intronic variant in TACC2 (transforming acidic coiled-coil-containing 2) (P = 4.2 × 10 ). TACC2, encoding a cytoskeleton-related protein, is highly expressed in skeletal muscle, and is reported as a target of myotonic dystrophy 1-associated splicing alterations. These suggest that changes in TACC2 expression are associated with variations in muscle strength in older people. The association was consistently observed in young and middle-aged subjects. Our findings would shed light on genetic components of lower limb muscle strength and indicate TACC2 as a potential therapeutic target for sarcopenia.