Genetics of neuroticism

Authored by Robert Chen • 
July 10, 2016
 • 2 min read

Known associations of genetic variants are shown below. Here, genes with an association with neuroticism are shown. A genetic variant may have a high association of propensity (i.e., odds ratio > 1) for neuroticism. On the other hand, a genetic variant that has an association of protection (i.e., odds ratio < 1), would confer higher propensity for positivity.

Genetic associations

There are a number of candidate genes that may be implicated in traits for neuroticism, discovered by GWAS studies. Future research should dive into dissecting out variants at these targets:

  • LCE3C (SNPs: rs12067374)1
  • POLR3A (SNPs: rs7905170)1
  • LMAN1L (SNPs: rs11634474)1
  • ULK3 (SNPs: rs936229)1
  • SCAMP2 (SNPs: rs37650661, rs18699591, rs116309181) There are several genes in linkage disequilibrium with SCAMP2, which may also play a role in modulating neuroticism: C15orf17, MPI, ULK3, COX5A.1
  • MAGI1 (SNPs: rs358557372) MAGI1 is also known to be associated with bipolar disorder, schizophrenia and episodicity in major depressive disorder.3,4,5
  • PTPRF (SNPs: rs20395286,7, rs112108646, rs108902516, rs66875716)
  • SORCS3 (SNPs: rs29264586)
  • TMEM16D (SNPs: rs16068656)
  • SHROOM3 (SNPs: rs125130136)
  • BCAS3 (SNPs: rs3625846)
  • SNAP25 (SNPs: rs3625847), which encodes synaptosomal-associated protein of 25 kDa7
  • TMEM16D (SNPs: rs18497107)
  1. Luciano, M., Huffman, J. E., Arias‐Vásquez, A., Vinkhuyzen, A. A., Middeldorp, C. M., Giegling, I., ... & Ke, X. (2012). Genome‐wide association uncovers shared genetic effects among personality traits and mood states. American Journal of Medical Genetics part B: Neuropsychiatric Genetics, 159(6), 684-695.

  2. De Moor, M. H., Van Den Berg, S. M., Verweij, K. J., Krueger, R. F., Luciano, M., Vasquez, A. A., ... & Gordon, S. D. (2015). Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with major depressive disorder. JAMA psychiatry, 72(7), 642-650.

  3. Karlsson, R., Graae, L., Lekman, M., Wang, D., Favis, R., Axelsson, T., ... & Paddock, S. (2012). MAGI1 copy number variation in bipolar affective disorder and schizophrenia. Biological psychiatry, 71(10), 922-930.

  4. Ferentinos, P., Rivera, M., Ising, M., Spain, S. L., Cohen-Woods, S., Butler, A. W., ... & Jones, I. (2014). Investigating the genetic variation underlying episodicity in major depressive disorder: Suggestive evidence for a bipolar contribution. Journal of affective disorders, 155, 81-89.

  5. Etain, B., Mathieu, F., Rietschel, M., Maier, W., Albus, M., Mckeon, P., ... & Bellivier, F. (2006). Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14. Molecular psychiatry, 11(7), 685-694.

  6. Bae, H. T., Sebastiani, P., Sun, J. X., Andersen, S. L., Daw, E. W., Terracciano, A., ... & Perls, T. T. (2013). Genome-wide association study of personality traits in the long life family study. Frontiers in genetics, 4.

  7. Terracciano, A., Sanna, S., Uda, M., Deiana, B., Usala, G., Busonero, F., ... & Distel, M. A. (2010). Genome-wide association scan for five major dimensions of personality. Molecular psychiatry, 15(6), 647-656.

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