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

      Linked Article

      • Antidepressant Response and Polygenes
        Biological PsychiatryVol. 73Issue 7
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          The goal of pharmacogenetics, to tailor drug treatments to patients based on molecular genetic markers, is fundamentally premised on drug responses being heritable traits. For studies of disease risk, the traditional genetic-epidemiologic approaches of twin and family studies have convincingly demonstrated a heritable basis for most diseases, motivating subsequent waves of molecular genetic studies to detect the specific genes. However, whether an individual’s response to a given drug is heritable has not, in general, been established.
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