{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:40:16Z","timestamp":1793302816585,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>\n                    Statin\u2010associated muscle symptoms (SAMS) are frequent adverse effects of statin therapy and have been hypothesized to result from impaired coenzyme Q10 (CoQ10) biosynthesis. Although genetic determinants of CoQ10 levels have been reported, genome\u2010wide association studies (GWASs) conducted specifically in statin users are lacking. Moreover, direct CoQ10 measurements are unavailable in large\u2010scale proteomic resources, necessitating suitable proxy biomarkers. COQ7, a key enzyme in the late steps of CoQ10 biosynthesis, was used as a proxy for CoQ10 biosynthetic capacity. We performed a GWAS of COQ7 protein levels in statin\u2010treated participants from the UK Biobank. The lead variant was evaluated for association with SAMS in an independent cohort of statin users from the All of Us, followed by replication in an independent SAMS cohort from the UK Biobank. Gene\u2013statin interaction analyses were conducted to assess statin\u2010specific genetic effects. In addition, polygenic risk score (PRS) analyses were performed using previously reported CoQ10\u2010associated variants from non\u2010statin\u2010specific cohorts. The GWAS identified the lead variant, rs66554427, with the A allele associated with lower COQ7 protein levels (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u2009\u22120.13, SE\u2009=\u20090.018,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20091.1\u2009\u00d7\u200910\n                    <jats:sup>\u221213<\/jats:sup>\n                    ). In the All of Us, the rs66554427 A allele was associated with an increased risk of SAMS (OR\u2009=\u20091.27, 95% CI: 1.16\u20131.39,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20095.16\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ). These findings were consistently replicated in the UK Biobank SAMS cohort (OR\u2009=\u20091.23, 95% CI: 1.06\u20131.43,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20096.89\u2009\u00d7\u200910\n                    <jats:sup>\u22123<\/jats:sup>\n                    ). Significant additive and multiplicative interactions between statin and rs66554427 were observed (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). PRS analyses further demonstrated that genetically predicted lower CoQ10 levels were associated with a higher risk of SAMS. Using COQ7 protein levels as a proxy for CoQ10 biosynthesis, we identified statin\u2010specific genetic susceptibility to SAMS and supported a causal role of impaired CoQ10 biosynthesis in SAMS.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70325","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T09:05:01Z","timestamp":1778490301000},"page":"475-483","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Uncovering Coenzyme\n                    <scp>Q10<\/scp>\n                    \u2010Related Genetic Determinants of Statin\u2010Associated Muscle Symptoms: Evidence from the\n                    <scp>UK<\/scp>\n                    Biobank and the All of Us Research Program"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6945-0127","authenticated-orcid":false,"given":"Da Hoon","family":"Lee","sequence":"first","affiliation":[{"name":"College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul Republic of Korea"},{"name":"College of Pharmacy Chungbuk National University  Cheongju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9162-2555","authenticated-orcid":false,"given":"Yoon\u2010A","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul Republic of Korea"},{"name":"Human\u2010Centered Artificial Intelligence Research Institute Ewha Womans University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6933-2642","authenticated-orcid":false,"given":"Yubin","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0662-0388","authenticated-orcid":false,"given":"Ji\u2010Min","family":"Han","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungbuk National University  Cheongju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9532-1581","authenticated-orcid":false,"given":"Kyung Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"College of Pharmacy Gachon University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5593-7672","authenticated-orcid":false,"given":"Myeong Gyu","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul Republic of Korea"},{"name":"Human\u2010Centered Artificial Intelligence Research Institute Ewha Womans University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0278-2563","authenticated-orcid":false,"given":"Hye Sun","family":"Gwak","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2001.tb00172.x"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvw006"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67394-1"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000677"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2681"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111687"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1017\/jns.2025.10043"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.04.009"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.01.032"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15183990"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/CRD.0000000000001135"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11060385"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40267-019-00677-x"},{"key":"e_1_2_10_14_1","first-page":"177","article-title":"COQ2 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