Scientists analysed the DNA of over 300,000 people and found many genes linked to neuroticism - characterised by feelings of anxiety, worry and guilt. The genes are also linked to depression.
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, said the researchers from the University of Edinburgh in the UK.
They analysed genetic information from a group of people aged from 39 to 73, whose levels of neuroticism had been measured by a personality questionnaire.
The researchers found that genes associated with neuroticism had some overlap with genes linked to a susceptibility to depression and some other psychiatric conditions.
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More than half of the genetic variations associated with neuroticism are expressed in the brain.
"These discoveries promise paths to understand the mechanisms whereby some people become depressed, and of broader human differences in happiness. They are a resource for those seeking treatments for depression," said Michelle Luciano, from the University of Edinburgh.
"For millennia it has been recognised that people have a greater or lesser tendency to feel low, worry, and experience other negative emotions," said Ian Deary, from the University of Edinburgh.
"These new results make a substantial contribution to solving that mystery by pointing to many specific places in the genome that are linked with neuroticism," Deary added.