{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T10:08:14Z","timestamp":1781863694847,"version":"3.54.5"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2017,12,11]],"date-time":"2017-12-11T00:00:00Z","timestamp":1512950400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,12,11]],"date-time":"2017-12-11T00:00:00Z","timestamp":1512950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the <jats:italic>HTT<\/jats:italic> gene. Although HD is frequently complicated by depression, it is still unknown to what extent common <jats:italic>HTT<\/jats:italic> CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between <jats:italic>HTT<\/jats:italic> CAG repeat size and depression risk in two well-characterized Dutch cohorts\u2500the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons\u2500including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and <jats:italic>HTT<\/jats:italic> CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (<jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.292 and <jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.006 for the linear and the quadratic term, respectively; both <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a <jats:italic>HTT<\/jats:italic> CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large <jats:italic>HTT<\/jats:italic> CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.<\/jats:p>","DOI":"10.1038\/s41398-017-0042-1","type":"journal-article","created":{"date-parts":[[2017,12,8]],"date-time":"2017-12-08T15:06:23Z","timestamp":1512745583000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Huntingtin gene repeat size variations affect risk of lifetime depression"],"prefix":"10.1038","volume":"7","author":[{"given":"Sarah L.","family":"Gardiner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine J.","family":"van Belzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merel W.","family":"Boogaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willeke M. 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