Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Sep;21(9):1290-7.
doi: 10.1038/mp.2015.165. Epub 2015 Oct 27.

Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder

J Song  1 , S E Bergen  1   2 , A Di Florio  3 , R Karlsson  1 , A Charney  4 , D M Ruderfer  4 , E A Stahl  4 ; Members of the International Cohort Collection for Bipolar Disorder (ICCBD); K D Chambert  2 , J L Moran  2 , K Gordon-Smith  5 , L Forty  3 , E K Green  6 , I Jones  3 , L Jones  5 , E M Scolnick  2 , P Sklar  4   7   8 , J W Smoller  9 , P Lichtenstein  1 , C Hultman  1 , N Craddock  3 , M Landén  1   10 , Jordan W Smoller, Roy H Perlis, Phil Hyoun Lee, Victor M Castro, Alison G Hoffnagle, Pamela Sklar, Eli A Stahl, Shaun M Purcell, Douglas M Ruderfer, Alexander W Charney, Panos Roussos, Carlos Pato Michele Pato, Helen Medeiros, Janet Sobel, Nick Craddock, Ian Jones, Liz Forty, Arianna Di Florio, Elaine Green, Lisa Jones, Katherine Gordon-Smith, Mikael Landen, Christina Hultman, Anders Jureus, Sarah Bergen, Steven McCarroll, Jennifer Moran, Jordan W Smoller, Kimberly Chambert, Richard A Belliveau
Affiliations

Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder

J Song et al. Mol Psychiatry. 2016 Sep.

Erratum in

  • Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder.
    Song J, Bergen SE, Di Florio A, Karlsson R, Charney A, Ruderfer DM, Stahl EA; Members of the International Cohort Collection for Bipolar Disorder (ICCBD); Chambert KD, Moran JL, Gordon-Smith K, Forty L, Green EK, Jones I, Jones L, Scolnick EM, Sklar P, Smoller JW, Lichtenstein P, Hultman C, Craddock N, Landén M. Song J, et al. Mol Psychiatry. 2017 Aug;22(8):1223. doi: 10.1038/mp.2016.246. Epub 2017 Feb 14. Mol Psychiatry. 2017. PMID: 28194006 Free PMC article.

Abstract

Lithium is the mainstay prophylactic treatment for bipolar disorder (BD), but treatment response varies considerably across individuals. Patients who respond well to lithium treatment might represent a relatively homogeneous subtype of this genetically and phenotypically diverse disorder. Here, we performed genome-wide association studies (GWAS) to identify (i) specific genetic variations influencing lithium response and (ii) genetic variants associated with risk for lithium-responsive BD. Patients with BD and controls were recruited from Sweden and the United Kingdom. GWAS were performed on 2698 patients with subjectively defined (self-reported) lithium response and 1176 patients with objectively defined (clinically documented) lithium response. We next conducted GWAS comparing lithium responders with healthy controls (1639 subjective responders and 8899 controls; 323 objective responders and 6684 controls). Meta-analyses of Swedish and UK results revealed no significant associations with lithium response within the bipolar subjects. However, when comparing lithium-responsive patients with controls, two imputed markers attained genome-wide significant associations, among which one was validated in confirmatory genotyping (rs116323614, P=2.74 × 10(-8)). It is an intronic single-nucleotide polymorphism (SNP) on chromosome 2q31.2 in the gene SEC14 and spectrin domains 1 (SESTD1), which encodes a protein involved in regulation of phospholipids. Phospholipids have been strongly implicated as lithium treatment targets. Furthermore, we estimated the proportion of variance for lithium-responsive BD explained by common variants ('SNP heritability') as 0.25 and 0.29 using two definitions of lithium response. Our results revealed a genetic variant in SESTD1 associated with risk for lithium-responsive BD, suggesting that the understanding of BD etiology could be furthered by focusing on this subtype of BD.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Sample ascertainment flow chart. (a) Subjectively defined lithium assessment. (b) Objectively defined lithium assessment.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Craddock N, Sklar P. Genetics of bipolar disorder. Lancet 2013; 381: 1654–1662. - PubMed
    1. Geddes JR, Miklowitz DJ. Treatment of bipolar disorder. Lancet 2013; 381: 1672–1682. - PMC - PubMed
    1. Garnham J, Munro A, Slaney C, Macdougall M, Passmore M, Duffy A et al. Prophylactic treatment response in bipolar disorder: results of a naturalistic observation study. J Affect Disord 2007; 104: 185–190. - PubMed
    1. Rybakowski JK. Lithium in neuropsychiatry: a 2010 update. World J Biol Psychiatry 2011; 12: 340–348. - PubMed
    1. McCarthy MJ, Leckband SG, Kelsoe JR. Pharmacogenetics of lithium response in bipolar disorder. Pharmacogenomics 2010; 11: 1439–1465. - PubMed

Publication types

MeSH terms