Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder

Access through your institution Buy or subscribe Substantial indirect evidence suggests overlap between bipolar disorder (BIP) and major depressive disorder (MDD). BIP and MDD have in common

major depressive episodes with BIP being distinguished by the additional presence of manic (bipolar 1) or hypomanic episodes (bipolar 2). Genetic epidemiological1 and genome-wide linkage

studies2 are also consistent with overlap between genetic risk factors for both disorders. In an attempt to identify common genetic risk factors, we conducted a meta-analysis combining data

from genome-wide association studies of BIP (4387 cases and 6209 controls)3 and MDD (1695 cases and 1761 controls).4 Ascertainment, diagnostic assessment, genotyping, quality control and

analysis are detailed elsewhere.3, 4 Both studies were conducted under the appropriate ethical approvals, and all subjects provided written informed consent. Briefly, BIP results are

obtained from a combined analysis of samples from the UK, the US and Ireland5, 6 with all subjects genotyped using Affymetrix 500K chips (Santa Clara, CA, USA). Most cases met criteria for

DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-IV) bipolar 1 (81%) with smaller numbers meeting criteria for bipolar 2 (16%), schizoaffective disorder/manic type (2%), or

bipolar NOS (not otherwise specified) (1%). After quality control, 1 769 948 single nucleotide polymorphisms (SNPs) were analyzed (18.7% were directly genotyped and the remainder were

imputed using HapMap2 CEU).7, 8 Cases meeting DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-IV) criteria for MDD were ascertained from clinical and community sources, and

controls at low liability for MDD were selected from a community sample.9 Genotyping was conducted by Perlegen using a 600K platform. After quality control (with slightly stricter thresholds

to maximize comparability), 1 893 617 SNPs were available (20.4% directly genotyped with the rest imputed using HapMap2 CEU).10 In both studies, SNPs were dropped for excessive missingness,

low minor allele frequencies and marked deviations from Hardy–Weinberg equilibrium. Subjects were removed for excessive missingness, unusual genome-wide heterozygosity, first- or

second-degree relation to any other subject, and if empirical ancestry deviated markedly from other subjects. There was no known subject overlap across studies (BIP subjects were from the

US, the UK and Ireland, and MDD subjects were from The Netherlands). This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution

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Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Genetics, University of North Carolina, Chapel Hill, NC, USA Y Liu & P F Sullivan * Department of

Psychological Medicine, University of Edinburgh, Edinburgh, UK D H Blackwood * Department of Psychological Medicine, Birmingham University, Birmingham, UK S Caesar, K Gordon-Smith & L

Jones * Department of Psychology, VU University Amsterdam, Amsterdam, The Netherlands E J C de Geus, J J Hottenga, G Willemsen & D I Boomsma * Department of Psychological Medicine,

Institute of Psychiatry, London, UK A Farmer & P McGuffin * Department of Genetics, Queensland Institute of Medical Research, Brisbane, Queensland, Australia M A R Ferreira * Department

of Psychological Medicine, Newcastle University, Newcastle, UK I N Ferrier * Department of Psychological Medicine, Cardiff University, Cardiff, UK C Fraser, E K Green, D Grozeva, M L

Hamshere, P A Holmans, I R Jones, G Kirov, V Moskvina, N Craddock, M C O'Donovan & M J Owen * Department of Psychological Medicine, University College London, London, UK H M Gurling

* Department of Psychiatry, VU University Medical Center Amsterdam, Amsterdam, The Netherlands P Heutink & W J Hoogendijk * Department of Biostatics, University of North Carolina,

Chapel Hill, NC, USA D Lin * Department of Psychological Medicine, University Medical Center, Groningen, The Netherlands W A Nolen * Department of Psychiatry, Massachusetts General Hospital,

Boston, MA, USA R H Perlis, J W Smoller, S Purcell & P Sklar * Department of Genetics, VU University Amsterdam, Amsterdam, The Netherlands D Posthuma, A B Smit & M Verhage *

Department of Genetics, Broad Institute, Cambridge, MA, USA E M Scolnick * Department of Psychiatry, VU University Medical Center Amsterdam, Amsterdam, The Netherlands J H Smit, R van Dyck 

& B W J H Penninx * Department of Psychological Medicine, Aberdeen University, Aberdeen, UK D St Clair * Department of Psychiatry, University of British Columbia, Vancouver, British

Columbia, Canada A H Young * Department of Psychology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands T Zandbelt Authors * Y Liu View author publications You can also

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CONSORTIUM CORRESPONDING AUTHOR Correspondence to P F Sullivan. ETHICS DECLARATIONS COMPETING INTERESTS In the interests of full disclosure, Dr Sullivan reports receiving unrestricted

research funding from Eli Lilly for genetic research in schizophrenia. Dr Perlis has received speaking or consulting fees from Astra Zeneca, Eli Lilly, GlaxoSmithKline, Pfizer, and Proteus,

LLC. Dr Nolen reports receiving unrestricted research funding and Speaker's fee from Astra Zeneca, Eli Lilly, GlaxoSmithKline, Pfizer, Servier and Wyeth. The other authors report no

conflicts. ADDITIONAL INFORMATION Supplementary Information accompanies the paper on the Molecular Psychiatry website SUPPLEMENTARY INFORMATION SUPPLEMENTARY MATERIAL (DOC 648 KB) RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Liu, Y., Blackwood, D., Caesar, S. _et al._ Meta-analysis of genome-wide association data of bipolar disorder and

major depressive disorder. _Mol Psychiatry_ 16, 2–4 (2011). https://doi.org/10.1038/mp.2009.107 Download citation * Published: 30 March 2010 * Issue Date: January 2011 * DOI:

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