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Neuroticism, a heritable personality trait associated with mental health, has been considered a risk factor for conversion from aMCI to AD. However, whether the neuroticism genetic risk could predict the conversion of aMCI and its underlying neural mechanisms is unclear. Neuroticism polygenic risk score (N\u2010PRS) was calculated in 278 aMCI patients with qualified genomic and neuroimaging data from ADNI. After 1\u2010year follow\u2010up, N\u2010PRS in patients of aMCI\u2010converted group was significantly greater than those in aMCI\u2010stable group. Logistic and Cox survival regression revealed that N\u2010PRS could significantly predict the early\u2010stage conversion risk from aMCI to AD. These results were well replicated in an internal dataset and an independent external dataset of 933 aMCI patients from the UK Biobank. One sample Mendelian randomization analyses confirmed a potentially causal association from higher N\u2010PRS to lower inferior parietal surface area to higher conversion risk of aMCI patients. These analyses indicated that neuroticism genetic risk may increase the conversion risk from aMCI to AD by impairing the inferior parietal structure.<\/jats:p>","DOI":"10.1002\/hbm.26709","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T07:54:59Z","timestamp":1715759699000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuroticism polygenic risk predicts conversion from mild cognitive impairment to Alzheimer's disease by impairing inferior parietal surface area"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3232-5526","authenticated-orcid":false,"given":"Qiaojun","family":"Li","sequence":"first","affiliation":[{"name":"College of Information Engineering Tianjin University of Commerce  Tianjin 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