Contribution of Common Genetic Variants to Antidepressant Response

Published:December 12, 2012DOI:


      Pharmacogenetic studies aiming to personalize the treatment of depression are based on the assumption that response to antidepressants is a heritable trait, but there is no compelling evidence to support this.


      We estimate the contribution of common genetic variation to antidepressant response with Genome-Wide Complex Trait Analysis in a combined sample of 2799 antidepressant-treated subjects with major depressive disorder and genome-wide genotype data.


      We find that common genetic variants explain 42% (SE = .180, p = .009) of individual differences in antidepressant response.


      These results suggest that response to antidepressants is a complex trait with substantial contribution from a large number of common genetic variants of small effect.

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        • O’Reilly R.L.
        • Bogue L.
        • Singh S.M.
        Pharmacogenetic response to antidepressants in a multicase family with affective disorder.
        Biol Psychiatry. 1994; 36: 467-471
        • Pare C.M.
        • Rees L.
        • Sainsbury M.J.
        Differentiation of two genetically specific types of depression by the response to anti-depressants.
        Lancet. 1962; 2: 1340-1343
        • Franchini L.
        • Serretti A.
        • Gasperini M.
        • Smeraldi E.
        Familial concordance of fluvoxamine response as a tool for differentiating mood disorder pedigrees.
        J Psychiatr Res. 1998; 32: 255-259
        • Yang J.
        • Lee S.H.
        • Goddard M.E.
        • Visscher P.M.
        GCTA: A tool for genome-wide complex trait analysis.
        Am J Hum Genet. 2011; 88: 76-82
        • Purcell S.
        • Neale B.
        • Todd-Brown K.
        • Thomas L.
        • Ferreira M.A.
        • Bender D.
        • et al.
        PLINK: A tool set for whole-genome association and population-based linkage analyses.
        Am J Hum Genet. 2007; 81: 559-575
        • Garriock H.A.
        • Kraft J.B.
        • Shyn S.I.
        • Peters E.J.
        • Yokoyama J.S.
        • Jenkins G.D.
        • et al.
        A genomewide association study of citalopram response in major depressive disorder.
        Biol Psychiatry. 2010; 67: 133-138
        • Wellcome Trust Case Control Consortium
        Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
        Nature. 2007; 447: 661-678
        • Uher R.
        • Perroud N.
        • Ng M.Y.
        • Hauser J.
        • Henigsberg N.
        • Maier W.
        • et al.
        Genome-wide pharmacogenetics of antidepressant response in the GENDEP project.
        Am J Psychiatry. 2010; 167: 555-564
        • Uher R.
        • Maier W.
        • Hauser J.
        • Marusic A.
        • Schmael C.
        • Mors O.
        • et al.
        Differential efficacy of escitalopram and nortriptyline on dimensional measures of depression.
        Br J Psychiatry. 2009; 194: 252-259
        • Yang J.
        • Benyamin B.
        • McEvoy B.P.
        • Gordon S.
        • Henders A.K.
        • Nyholt D.R.
        • et al.
        Common SNPs explain a large proportion of the heritability for human height.
        Nat Genet. 2010; 42: 565-569
        • Uher R.
        • Huezo-Diaz P.
        • Perroud N.
        • Smith R.
        • Rietschel M.
        • Mors O.
        • et al.
        Genetic predictors of response to antidepressants in the GENDEP project.
        Pharmacogenomics J. 2009; 9: 225-233
        • Purcell S.M.
        • Wray N.R.
        • Stone J.L.
        • Visscher P.M.
        • O’Donovan M.C.
        • Sullivan P.F.
        • et al.
        Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.
        Nature. 2009; 460: 748-752
        • Lee S.H.
        • Decandia T.R.
        • Ripke S.
        • Yang J.
        • Sullivan P.F.
        • Goddard M.E.
        • et al.
        Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs.
        Nat Genet. 2012; 44: 247-250
        • Davies G.
        • Tenesa A.
        • Payton A.
        • Yang J.
        • Harris S.E.
        • Liewald D.
        • et al.
        Genome-wide association studies establish that human intelligence is highly heritable and polygenic.
        Mol Psychiatry. 2011; 16: 996-1005