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ADHD\u2019s aetiology is complex, and evidence about its cause and risk factors is limited. We leveraged genetic data from genome-wide association studies (GWAS) and performed latent causal variable analyses using a hypothesis-free approach to infer causal associations between 1387 complex traits and ADHD. We identified 37 inferred potential causal associations with ADHD risk. Our results reveal that genetic variants associated with <jats:italic>iron deficiency anemia (ICD10)<\/jats:italic>, <jats:italic>obesity<\/jats:italic>, <jats:italic>type 2 diabetes, synovitis and tenosynovitis (ICD10)<\/jats:italic>, <jats:italic>polyarthritis (ICD10)<\/jats:italic>,<jats:italic> neck or shoulder pain<\/jats:italic>, and <jats:italic>substance use<\/jats:italic> in adults display partial genetic causality on ADHD risk in children. Genetic variants associated with ADHD have a partial genetic causality increasing the risk for <jats:italic>chronic obstructive pulmonary disease<\/jats:italic> and <jats:italic>carpal tunnel syndrome.<\/jats:italic> Protective factors for ADHD risk included genetic variants associated with the likelihood of participating in socially supportive and interactive activities. Our results show that genetic liability to multiple complex traits influences a higher risk for ADHD, highlighting the potential role of cardiometabolic phenotypes and physical pain in ADHD\u2019s aetiology. These findings have the potential to inform future clinical studies and development of interventions.<\/jats:p>","DOI":"10.1038\/s41598-021-01517-7","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T11:03:26Z","timestamp":1637319806000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Large-scale genetic investigation reveals genetic liability to multiple complex traits influencing a higher risk of ADHD"],"prefix":"10.1038","volume":"11","author":[{"given":"Luis M.","family":"Garc\u00eda-Mar\u00edn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adri\u00e1n I.","family":"Campos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Cu\u00e9llar-Partida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Medland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott H.","family":"Kollins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel E.","family":"Renter\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,11,19]]},"reference":[{"key":"1517_CR1","volume-title":"Attention Deficit Hyperactivity Disorder","author":"W Magnus","year":"2020","unstructured":"Magnus, W., Nazir, S., Anilkumar, A. 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He is now an employee of 23andMe Inc., and he may hold stock or stock options. All other authors declare having no conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22628"}}