Genome-wide association in bipolar

Gershon, Elliot S.; Liu, Chun Yu; Badner, Judith A.

doi:10.1038/sj.mp.4002117

Cited by 21 publications

(30 citation statements)

References 14 publications

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“…Following initial submission of parts of the analyses presented herein (e.g., based on three of the four bipolar versus control datasets), several (though not all) reports appeared that failed to identify any allele of any single nucleotide polymorphism (SNP) (''same SNP same allele'' analysis) that was strongly associated with bipolar disorder in each of the available bipolar versus control comparisons [Baum et al, 2008;Gershon et al, 2008;Sklar et al, 2008]. The analytic approach used both here and in the previously submitted manuscript is based on assumptions that polygenic underlying genetic architectures for vulnerabilities to bipolar disorder are likely to result in association signals of modest strength for allelic variants at any single SNP.…”

Section: Discussionmentioning

confidence: 96%

“…The individuals studied were of largely European genetic background and were collected in the United States, the United Kingdom, and Germany [McQueen et al, 2005;Baum et al, 2007;WellcomeTrustConsortium, 2007;Sklar et al, 2008]. Most of these analyses have sought, and failed to identify, the same alleles of specific single nucleotide polymorphisms (SNP) (''same SNP same allele'' analysis) that were strongly associated with bipolar disorder in each of these multiple samples [Baum et al, 2008;Gershon et al, 2008;Sklar et al, 2008], although a recent analysis has identified some SNPs that display some of these properties .…”

Section: Introductionmentioning

confidence: 99%

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Convergent genome wide association results for bipolar disorder and substance dependence

Johnson

Drgon

McMahon³

et al. 2009

American J of Med Genetics Pt B

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Twin studies document substantial heritability for substance dependence and bipolar disorder [Shih et al. (2004); Uhl et al. (2008a)]. Individuals with bipolar disorder display substance use disorders at rates that are much higher than those in the general population [Krishnan (2005)]. We would thus predict: 1) substantial overlap between different genome wide association (GWA) studies of bipolar disorder 2) significant overlap between results from bipolar disorder and substance dependence. Recent GWA studies [Baum et al. (2007); Sklar et al. (2008); Uhl et al. (2008a); Wellcome Trust Consortium (2007)] allow us to test these ideas, although 1) these datasets display difficult features that include use of differing sets of SNPs, likely polygenic genetics, likely differences in linkage disequilibrium between samples, heterogeneity both between and within loci and 2) several, though not all, reports have failed to identify any allele of any single nucleotide polymorphism (SNP) ("same SNP same allele") that is reproducibly associated with bipolar disorder with "genome wide" significance. We now report analyses that identify clustered, P < 0.05 SNPs within genes that overlap between the bipolar samples (Monte Carlo P < 0.00001). Overlapping data from at least three of these studies identify 69 genes. 23 of these genes also contain overlapping clusters of nominally-positive SNPs for substance dependence. Variants in these "addiction/bipolar" genes are candidates to influence the brain in ways that manifest as enhanced vulnerabilites to both substance dependence and bipolar disorder.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Convergent genome wide association results for bipolar disorder and substance dependence

Johnson

Drgon

McMahon³

et al. 2009

American J of Med Genetics Pt B

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“…As discussed by Gershon and others [2008], multiple linkage scans, including the major meta-analyses of linkage results in bipolar disorder, show discrepancies from GWAS findings. Moreover, there is a lack of clear correspondence in results among the published GWAS [Gershon and others 2008].…”

Section: Discussionmentioning

confidence: 99%

Fine mapping of candidate regions for bipolar disorder provides strong evidence for susceptibility loci on chromosomes 7q

Xu¹,

Cheng²,

Juo³

et al. 2010

Am. J. Med. Genet.

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Genomewide scans of bipolar disorder (BP) have not produced consistent linkage findings. Follow-up studies using enlarged samples and enhanced marker density can bolster or refute claims of linkage and pave the way to gene discovery. We conducted linkage and association analyses, using a ~3-cM density map of 10 candidate regions, in a large BP pedigree sample (865 individuals from 56 pedigrees). The candidate regions were identified in a previous 10-cM genome-wide scan using a subset of this sample (373 individuals from 40 pedigrees). The present sample consists of the expanded original pedigrees ('core' pedigrees) and 16 additional pedigrees. We obtained experiment-wide significant linkage on chromosome 7q34 (LOD score 3.53, p<0.001), substantially stronger than that observed in the genome-wide scan. Support for linkage was sustained on chromosomes 2p13, 4q31, 8q13, 13q32, 14q21 and 17q11, though at a more modest level. Family-based association analysis was consistent with the linkage results at all regions with linkage evidence, except 4q an 8q, but the results fell short of statistical significance. Three of the previously implicated regions -9q31, 10q21 and 10q24 -showed substantial reduction in evidence of linkage. Our results strongly support 7q34 as a region harboring susceptibility locus for BP. Somewhat lesser, yet notable support was obtained for 2p13, 4q31, 8q13, 13q32, 14q21 and 17q11. These regions could be considered prime candidates for future gene finding efforts.

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“…Perhaps a bit of both, but it is vital to remember that the GWAS model is predicated on common ancient variants as the mediators of risk. This model already seems to be on less solid ground for SZ and BP [19,20]. At face value, there is little convincing overlap in associations between the published BP studies [15 ], but a preliminary meta-analysis of the WTCCC [12 ] and Baum et al [14] gives both some comfort and reason to query the underlying philosophy [21].…”

Section: Genome Wide Association Studies (Gwas)mentioning

confidence: 97%

Genetic causality in schizophrenia and bipolar disorder: out with the old and in with the new

Porteous

2008

Current Opinion in Genetics & Development

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Genome-wide association in bipolar

Cited by 21 publications

References 14 publications

Convergent genome wide association results for bipolar disorder and substance dependence

Convergent genome wide association results for bipolar disorder and substance dependence

Fine mapping of candidate regions for bipolar disorder provides strong evidence for susceptibility loci on chromosomes 7q

Genetic causality in schizophrenia and bipolar disorder: out with the old and in with the new

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