Recurrent major depression and right hippocampal volume: A bivariate linkage and association study

Samuel R. Mathias, Emma E.M. Knowles, Jack W. Kent, D. Reese Mckay, Joanne E Curran, Marcio A.A. de Almeida, Thomas D. Dyer, Harald HH Goring, Rene L. Olvera, Ravindranath Duggirala, Peter T. Fox, Laura A Almasy, John C Blangero, David C. Glahn

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Previous work has shown that the hippocampus is smaller in the brains of individuals suffering from major depressive disorder (MDD) than those of healthy controls. Moreover, right hippocampal volume specifically has been found to predict the probability of subsequent depressive episodes. This study explored the utility of right hippocampal volume as an endophenotype of recurrent MDD (rMDD). We observed a significant genetic correlation between the two traits in a large sample of Mexican American individuals from extended pedigrees (ρg = -0.34, p = 0.013). A bivariate linkage scan revealed a significant pleiotropic quantitative trait locus on chromosome 18p11.31-32 (LOD = 3.61). Bivariate association analysis conducted under the linkage peak revealed a variant (rs574972) within an intron of the gene SMCHD1 meeting the corrected significance level (χ2 = 19.0, p = 7.4 × 10-5). Univariate association analyses of each phenotype separately revealed that the same variant was significant for right hippocampal volume alone, and also revealed a suggestively significant variant (rs12455524) within the gene DLGAP1 for rMDD alone. The results implicate right-hemisphere hippocampal volume as a possible endophenotype of rMDD, and in so doing highlight a potential gene of interest for rMDD risk. Hum Brain Mapp 37:191-202, 2016.

Original languageEnglish (US)
Pages (from-to)191-202
Number of pages12
JournalHuman Brain Mapping
Issue number1
StatePublished - Jan 1 2016


  • Depression
  • Genome-wide association
  • Hippocampus
  • Linkage

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology


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