Researchers have long known that neuroticism—a personality trait characterized by a tendency toward negative emotions as well as anxiety, anger, envy, guilt and depression—is influenced by genetics. No specific genes have yet been linked to neuroticism, but the results of two large genetic studies reported in April will help narrow the search. The studies, which together analyzed genetic data from hundreds of thousands of people, have identified up to 11 neuroticism-associated sites in the genome. Some neuroticism-associated sites were also linked to depression.

One study, reported April 18 in Nature Genetics, analyzed the genomes of nearly 300,000 people, looking for genetic factors associated with neuroticism, as well as factors associated with depression or a general sense of well-being.

The large-scale analysis involved 190 scientists, including NARSAD 2015 Young Investigator Jacob Gratten, Ph.D., at the University of Queensland; 2004 Young Investigator and 2009 Independent Investigator Lars Bertram, M.D., at the Max-Planck Institute for Molecular Genetics; 2011 Distinguished Investigator Dorret I. Boomsma, Ph.D., at Vrije Universiteit; and 2014 Young Investigator Shun-Chiao Chang, Sc.D. at Brigham and Women’s Hospital. Robert F. Krueger Ph.D., at the University of Minnesota; Jonathan P. Beauchamp, Ph.D., at Harvard University; Philipp D. Koellinger, Ph.D., at the Erasmus Research Institute of Management; Daniel J. Benjamin, Ph.D., at the University of Southern California, Meike Bartels, Ph.D., at Vrije Universiteit; and David Cesarini, Ph.D., at New York University, led the team.

That study identified 11 genetic variants associated with neuroticism, as well as two associated with depressive symptoms and three linked to subjective well-being. No single genetic factor establishes a person’s sense of well-being or determines whether he or she will expression depression or neuroticism, the researchers note. In fact, the gene variants they identified account for only a small part of the genetic influence over these traits—suggesting a great many more genes are involved.

Using a subset of the same data, from 106,000 people, a second team identified nine neuroticism-associated sites. Some of these sites are large—the one with the strongest link to neuroticism spans at least 36 genes.

That study, reported April 12 in the journal Molecular Psychiatry, was led by 2012 Lieber Prizewinner Michael O’Donovan, M.D., Ph.D., at Cardiff University, and Ian Deary at the University of Edinburgh, and included NARSAD 2014 Independent Investigator Daniel J. Smith, M.D., at Cardiff University; and 2008 Distinguished Investigator David J. Porteous, Ph.D., and 2010 Independent Investigator Andrew M. McIntosh, M.D., both at the University of Edinburgh.

Both studies found overlap between the genetic factors associated with neuroticism and those associated with depression. (One study analyzed gene variants associated with major depression, whereas the other looked for variants associated with depressive symptoms.) Neuroticism-associated genetic variants were also more common among people with anxiety disorders.