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We analysed the DNA of over 300,000 people from UK Biobank (aged from 39 to 73) and found many genetic variants linked to neuroticism a personality trait characterised by feelings of anxiety, worry and guilt. Our genome-wide association analysis uncovered 116 gene variations linked to neuroticism, 15 of these replicated in a large independent sample. We also found that genes associated with neuroticism had some overlap with genes linked to a susceptibility to depression and some other psychiatric conditions. The findings help shed light on the causes of depression which affects one in five people and could provide information to help better diagnosis and treatment for individuals. More than half of the genetic variations associated with neuroticism were found to be expressed in the brain.