Race, genetic ancestry and response to antidepressant treatment for major depression

Eleanor Murphy, Liping Hou, Brion Maher, Girma Woldehawariat, Layla Kassem, Nirmala Akula, Gonzalo Laje, Francis J. McMahon

Research output: Contribution to journalArticle

Abstract

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials.

Original languageEnglish (US)
Pages (from-to)2598-2606
Number of pages9
JournalNeuropsychopharmacology
Volume38
Issue number13
DOIs
StatePublished - Dec 2013

Fingerprint

Antidepressive Agents
Depression
Citalopram
Single Nucleotide Polymorphism
Therapeutics
Genetic Models
African Americans
Anxiety
Genome
Equipment and Supplies
DNA
Pharmaceutical Preparations

Keywords

  • African Americans
  • Ethnicity
  • Genetics
  • Pharmacology
  • SSRI

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Murphy, E., Hou, L., Maher, B., Woldehawariat, G., Kassem, L., Akula, N., ... McMahon, F. J. (2013). Race, genetic ancestry and response to antidepressant treatment for major depression. Neuropsychopharmacology, 38(13), 2598-2606. https://doi.org/10.1038/npp.2013.166

Race, genetic ancestry and response to antidepressant treatment for major depression. / Murphy, Eleanor; Hou, Liping; Maher, Brion; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J.

In: Neuropsychopharmacology, Vol. 38, No. 13, 12.2013, p. 2598-2606.

Research output: Contribution to journalArticle

Murphy, E, Hou, L, Maher, B, Woldehawariat, G, Kassem, L, Akula, N, Laje, G & McMahon, FJ 2013, 'Race, genetic ancestry and response to antidepressant treatment for major depression', Neuropsychopharmacology, vol. 38, no. 13, pp. 2598-2606. https://doi.org/10.1038/npp.2013.166
Murphy, Eleanor ; Hou, Liping ; Maher, Brion ; Woldehawariat, Girma ; Kassem, Layla ; Akula, Nirmala ; Laje, Gonzalo ; McMahon, Francis J. / Race, genetic ancestry and response to antidepressant treatment for major depression. In: Neuropsychopharmacology. 2013 ; Vol. 38, No. 13. pp. 2598-2606.
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