Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder
dc.contributor.author | Song, J | |
dc.contributor.author | Bergen, SE | |
dc.contributor.author | Di Florio, A | |
dc.contributor.author | Karlsson, R | |
dc.contributor.author | Charney, A | |
dc.contributor.author | Ruderfer, DM | |
dc.contributor.author | Stahl, EA | |
dc.contributor.author | Chambert, KD | |
dc.contributor.author | Moran, JL | |
dc.contributor.author | Gordon-Smith, K | |
dc.contributor.author | Forty, L | |
dc.contributor.author | Green, Elaine | |
dc.contributor.author | Jones, I | |
dc.contributor.author | Jones, L | |
dc.contributor.author | Scolnick, EM | |
dc.contributor.author | Sklar, P | |
dc.contributor.author | Smoller, JW | |
dc.contributor.author | Lichtenstein, P | |
dc.contributor.author | Hultman, C | |
dc.contributor.author | Craddock, N | |
dc.contributor.author | Landén, M | |
dc.contributor.author | Smoller, JW | |
dc.contributor.author | Perlis, RH | |
dc.contributor.author | Lee, PH | |
dc.contributor.author | Castro, VM | |
dc.contributor.author | Hoffnagle, AG | |
dc.contributor.author | Sklar, P | |
dc.contributor.author | Stahl, EA | |
dc.contributor.author | Purcell, SM | |
dc.contributor.author | Ruderfer, DM | |
dc.contributor.author | Charney, AW | |
dc.contributor.author | Roussos, P | |
dc.contributor.author | Michele Pato, CP | |
dc.contributor.author | Medeiros, H | |
dc.contributor.author | Sobel, J | |
dc.contributor.author | Craddock, N | |
dc.contributor.author | Jones, I | |
dc.contributor.author | Forty, L | |
dc.contributor.author | Florio, AD | |
dc.contributor.author | Green, E | |
dc.contributor.author | Jones, L | |
dc.contributor.author | Gordon-Smith, K | |
dc.contributor.author | Landen, M | |
dc.contributor.author | Hultman, C | |
dc.contributor.author | Jureus, A | |
dc.contributor.author | Bergen, S | |
dc.contributor.author | McCarroll, S | |
dc.contributor.author | Moran, J | |
dc.contributor.author | Smoller, JW | |
dc.contributor.author | Chambert, K | |
dc.contributor.author | Belliveau, RA | |
dc.date.accessioned | 2016-11-29T15:10:33Z | |
dc.date.available | 2016-11-29T15:10:33Z | |
dc.date.issued | 2016-09 | |
dc.identifier.issn | 1359-4184 | |
dc.identifier.issn | 1476-5578 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/8046 | |
dc.description.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. | |
dc.format.extent | 1290-1297 | |
dc.format.medium | Print-Electronic | |
dc.language | en | |
dc.language.iso | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.subject | Adult | |
dc.subject | Antimanic Agents | |
dc.subject | Biomarkers, Pharmacological | |
dc.subject | Bipolar Disorder | |
dc.subject | Carrier Proteins | |
dc.subject | Female | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Genetic Variation | |
dc.subject | Genome-Wide Association Study | |
dc.subject | Genotype | |
dc.subject | Humans | |
dc.subject | Lithium | |
dc.subject | Lithium Compounds | |
dc.subject | Male | |
dc.subject | Middle Aged | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Risk Factors | |
dc.subject | Self Report | |
dc.subject | Sweden | |
dc.subject | United Kingdom | |
dc.title | Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, N.I.H., Extramural | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000382328900018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 9 | |
plymouth.volume | 21 | |
plymouth.publication-status | Published | |
plymouth.journal | Molecular Psychiatry | |
dc.identifier.doi | 10.1038/mp.2015.165 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/Research Groups | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED) | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR | |
plymouth.organisational-group | /Plymouth/Users by role | |
dc.publisher.place | England | |
dcterms.dateAccepted | 2015-09-24 | |
dc.identifier.eissn | 1476-5578 | |
dc.rights.embargoperiod | No embargo | |
rioxxterms.versionofrecord | 10.1038/mp.2015.165 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2016-09 | |
rioxxterms.type | Journal Article/Review |