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Genet."],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Leveraging genome-wide association statistics generated from a large study of amyotrophic lateral sclerosis (ALS; 29,612 cases and 122,656 controls) and UK Biobank (UKB; 4,024 phenotypes, up to 361,194 participants), we conducted a phenome-wide analysis of ALS genetic liability and identified 46 genetically correlated traits, such as fluid intelligence score (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>g<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u2009\u2212\u00a00.21,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20091.74\u2009\u00d7\u200910\n                    <jats:sup>\u20136<\/jats:sup>\n                    ), \"spending time in pub or social club\u201d (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>g<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u20090.24,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20092.77\u2009\u00d7\u200910\n                    <jats:sup>\u20136<\/jats:sup>\n                    ), non-work related walking (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>g<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u2009\u2212\u00a00.25,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20091.95\u2009\u00d7\u200910\n                    <jats:sup>\u20136<\/jats:sup>\n                    ), college education (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>g<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u2009\u2212\u00a00.15,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20097.08\u2009\u00d7\u200910\n                    <jats:sup>\u20135<\/jats:sup>\n                    ), \u201cever diagnosed with panic attacks (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>g<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u20090.39,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20094.24\u2009\u00d7\u200910\n                    <jats:sup>\u20135<\/jats:sup>\n                    ), and \u201cself-reported other gastritis including duodenitis\u201d (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>g<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u20090.28,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20091.4\u2009\u00d7\u200910\n                    <jats:sup>\u20133<\/jats:sup>\n                    ). To assess the putative directionality of these genetic correlations, we conducted a latent causal variable analysis, identifying significant genetic causality proportions (g\u0109p) linking ALS genetic liability to seven traits. While the genetic component of \u201cself-reported other gastritis including duodenitis\" showed a causal effect on ALS (g\u0109p\u2009=\u20090.50,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20091.26\u2009\u00d7\u200910\n                    <jats:sup>\u201329<\/jats:sup>\n                    ), the genetic liability to ALS is potentially causal for multiple traits, also including an effect on \"ever being diagnosed with panic attacks\u201d (g\u0109p\u2009=\u20090.79,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20095.011\u2009\u00d7\u200910\n                    <jats:sup>\u201315<\/jats:sup>\n                    ) and inverse effects on \u201cother leisure\/social group activities\u201d (g\u0109p\u2009=\u20090.66,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20091\u2009\u00d7\u200910\n                    <jats:sup>\u20134<\/jats:sup>\n                    ) and prospective memory result (g\u0109p\u2009=\u20090.35,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.005). Our subsequent Mendelian randomization analysis indicated that some of these associations may be due to bidirectional effects. In conclusion, this phenome-wide investigation of ALS polygenic architecture highlights the widespread pleiotropy linking this disorder with several health domains.\n                  <\/jats:p>","DOI":"10.1007\/s00439-023-02525-5","type":"journal-article","created":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T04:05:36Z","timestamp":1676088336000},"page":"1173-1183","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Phenome-wide genetic-correlation analysis and genetically informed causal inference of amyotrophic lateral sclerosis"],"prefix":"10.1007","volume":"142","author":[{"given":"Salvatore","family":"D\u2019Antona","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gita A.","family":"Pathak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Koller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo","family":"Porro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0745-6046","authenticated-orcid":false,"given":"Renato","family":"Polimanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,11]]},"reference":[{"key":"2525_CR1","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1159\/000108917","volume":"29","author":"K Abhinav","year":"2007","unstructured":"Abhinav K, Stanton B, Johnston C, Hardstaff J, Orrell RW, Howard R, Clarke J, Sakel M, Ampong MA, Shaw CE, Leigh PN, Al-Chalabi A (2007) Amyotrophic lateral sclerosis in South-East England: a population-based study. 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