Leo Sher, M.D.

Our research report, “Pleiotropy of the serotonin transporter gene for seasonality and neuroticism” was published 20 years ago in the September 2000 issue of Psychiatric Genetics (1).

Pleiotropy refers to the ability of a single gene to influence multiple traits. A polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) was found to be associated both with the personality trait of neuroticism and with seasonal changes in mood and behavior, or seasonality. 5-HTTLPR is a variation in the promoter region of the serotonin transporter gene (SLC6A4).

We measured 5-HTTLPR genotypes and both psychological traits in 236 healthy volunteers. The 5-HTTLPR was significantly associated with both neuroticism and seasonality. The results indicated that the 5-HTTLPR contributions to variation in the two traits are largely independent. Approximately three-quarters of the effect of the gene on seasonality are not related to its effects on neuroticism. The gene has a larger effect on the covariation between neuroticism and seasonality than it does on either trait alone. Sibling-pair analysis confirmed that the effects of the serotonin transporter gene are due to genetic pleiotropy rather than population stratification.

Reference

1. Sher L, Greenberg BD, Murphy DL, Rosenthal NE, Sirota LA, Hamer DH. Pleiotropy of the serotonin transporter gene for seasonality and neuroticism. Psychiatr Genet. 2000 Sep;10(3):125-30. doi: 10.1097/00041444-200010030-00004. PMID: 11204348.