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Genome-wide associa...
Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder
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- Song, J. (författare)
- Karolinska Institutet
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- Bergen, S. E. (författare)
- Karolinska Institutet
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Di Florio, A. (författare)
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- Karlsson, R. (författare)
- Karolinska Institutet
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Charney, A. (författare)
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Ruderfer, D. M. (författare)
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Stahl, E. A. (författare)
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Chambert, K. D. (författare)
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- Moran, J. L. (författare)
- Karolinska Institutet
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Gordon-Smith, K. (författare)
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Forty, L. (författare)
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Green, E. K. (författare)
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Jones, I. (författare)
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Jones, L. (författare)
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Scolnick, E. M. (författare)
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Sklar, P. (författare)
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Smoller, J. W. (författare)
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- Lichtenstein, P. (författare)
- Karolinska Institutet
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- Hultman, C. (författare)
- Karolinska Institutet
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Craddock, N. (författare)
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- Landén, Mikael, 1966 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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(creator_code:org_t)
- 2015-10-27
- 2016
- Engelska.
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:9, s. 1290-1297
- Relaterad länk:
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https://www.nature.c...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 x 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
Nyckelord
- receptor potential channels
- neurotrophic factor gene
- prophylactic
- lithium
- maintenance treatment
- japanese patients
- trpc5 channels
- brain
- mechanism
- polymorphism
- schizophrenia
- Biochemistry & Molecular Biology
- Neurosciences & Neurology
- Psychiatry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Song, J.
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Bergen, S. E.
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Di Florio, A.
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Karlsson, R.
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Charney, A.
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Ruderfer, D. M.
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visa fler...
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Stahl, E. A.
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Chambert, K. D.
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Moran, J. L.
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Gordon-Smith, K.
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Forty, L.
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Green, E. K.
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Jones, I.
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Jones, L.
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Scolnick, E. M.
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Sklar, P.
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Smoller, J. W.
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Lichtenstein, P.
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Hultman, C.
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Craddock, N.
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Landén, Mikael, ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Psykiatri
- Artiklar i publikationen
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Molecular Psychi ...
- Av lärosätet
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Göteborgs universitet
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Karolinska Institutet