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Genome-wide association studies, however, implicate several novel single-nucleotide polymorphisms with weak but replicable effects and unclarified mechanisms. We investigated the effect of rs1106634 of the ATPV1B2 gene encoding the vacuolar H+ATPase on lifetime and current depression and the possible mediating role of neuroticism by logistic and linear regression in a white European general sample of 2226 subjects. Association of rs1106634 with performance on frontal (Stockings of Cambridge (SOC)) and hippocampal-dependent (paired associates learning (PAL)) cognitive tasks was investigated in multivariate general linear models in a smaller subsample. The ATP6V1B2 rs1106634 A allele had a significant effect on lifetime but not on current depression. The effect of the A allele on lifetime depression was not mediated by neuroticism. The A allele influenced performance on the PAL but not on the SOC test. We conclude that the effects of variation in the vacuolar ATPase may point to a new molecular mechanism that influences the long-term development of depression. This mechanism may involve dysfunction specifically in hippocampal circuitry and cognitive impairment that characterizes recurrent and chronic depression.<\/jats:p>","DOI":"10.1038\/tp.2016.221","type":"journal-article","created":{"date-parts":[[2016,11,8]],"date-time":"2016-11-08T14:44:34Z","timestamp":1478616274000},"page":"e945-e945","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Association of ATP6V1B2 rs1106634 with lifetime risk of depression and hippocampal neurocognitive deficits: possible novel mechanisms in the etiopathology of depression"],"prefix":"10.1038","volume":"6","author":[{"given":"X","family":"Gonda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Eszlari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I M","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J F W","family":"Deakin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Bagdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Juhasz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,8]]},"reference":[{"key":"BFtp2016221_CR1","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1016\/S0140-6736(96)07495-8","volume":"349","author":"CJ Murray","year":"1997","unstructured":"Murray CJ, Lopez AD . 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