Linkage of Bipolar Disorder to Chromosome 18q and the Validity of Bipolar II Disorder

McMahon, Francis J.

doi:10.1001/archpsyc.58.11.1025

Cited by 95 publications

(68 citation statements)

References 31 publications

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“…An analysis in a subset of these pedigrees indicates that siblings with BPII disorder contribute a significant portion of the increased allelic sharing. 36 Several other studies of bipolar disorder have implicated 18q, 15,37-39 but as might be expected with a complex disorder, 40 not all studies have replicated this finding. 38,[41][42][43] The next strongest finding in the present study was at D4S1629 on 4q32 (NPL ¼ 2.8, Po0.004) using the BPUP affection model, which coincides with a region identified by Ekholm et al 44 Ekholm et al 44 studied 41 Finnish pedigrees and reported a Z max of 3.3 at D4S1629.…”

Section: Discussionmentioning

confidence: 95%

Genome-wide scan of bipolar disorder in 65 pedigrees: supportive evidence for linkage at 8q24, 18q22, 4q32, 2p12, and 13q12

et al. 2003

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The purpose of this study was to assess 65 pedigrees ascertained through a Bipolar I (BPI) proband for evidence of linkage, using nonparametric methods in a genome-wide scan and for possible parent of origin effect using several analytical methods. We identified 15 loci with nominally significant evidence for increased allele sharing among affected relative pairs. Eight of these regions, at 8q24, 18q22, 4q32, 13q12, 4q35, 10q26, 2p12, and 12q24, directly overlap with previously reported evidence of linkage to bipolar disorder. Five regions at 20p13, 2p22, 14q23, 9p13, and 1q41 are within several Mb of previously reported regions. We report our findings in rank order and the top five markers had an NPL42.5. The peak finding in these regions were D8S256 at 8q24, NPL 3.13; D18S878 at 18q22, NPL 2.90; D4S1629 at 4q32, NPL 2.80; D2S99 at 2p12, NPL 2.54; and D13S1493 at 13q12, NPL 2.53. No locus produced statistically significant evidence for linkage at the genome-wide level. The parent of origin effect was studied and consistent with our previous findings, evidence for a locus on 18q22 was predominantly from families wherein the father or paternal lineage was affected. There was evidence consistent with paternal imprinting at the loci on 13q12 and 1q41.

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Section: Discussionmentioning

confidence: 95%

Genome-wide scan of bipolar disorder in 65 pedigrees: supportive evidence for linkage at 8q24, 18q22, 4q32, 2p12, and 13q12

et al. 2003

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“…The familial nature of hypomania has raised questions whether BDII is a distinct category. 33,35 Congruent with this view are the findings of McMahon et al 36 showing that families with BDII cases had the strongest evidence of linkage to chromosome 18q21-23 markers.…”

Section: Diagnosis Of Bdmentioning

confidence: 95%

The phenotypes of bipolar disorder: relevance for genetic investigations

2005

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The search for susceptibility genes for bipolar disorder (BD) depends on appropriate definitions of the phenotype. In this paper, we review data on diagnosis and clinical features of BD that could be used in genetic studies to better characterize patients or to define homogeneous subgroups. Clinical symptoms, long-term course, comorbid conditions, and response to prophylactic treatment may define groups associated with more or less specific loci. One such group is characterized by symptoms of psychosis and linkage to 13q and 22q. A second group includes mainly bipolar II patients with comorbid panic disorder, rapid mood switching, and evidence of chromosome 18 linkage. A third group comprises typical BD with an episodic course and favourable response to lithium prophylaxis. Reproducibility of cognitive deficits across studies raises the possibility of using cognitive profiles as endophenotypes of BD, with deficits in verbal explicit memory and executive function commonly reported. Brain imaging provides a more ambiguous data set consistent with heterogeneity of the illness. Keywords: bipolar disorder; genetics; endophenotype; neurocognitive function; brain imaging Bipolar disorder (BD) has a genetic basis with heritability of at least 80%. 1 A number of studies have attempted to map the susceptibility loci giving evidence of linkage in multiple genomic regions. In particular, findings in 4p, 4q, 8q, 10p, 12q24, 13q, 18p, 18q, 21q, and 22q have been supported by more than one study. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] However, these studies have not identified any specific genes, and a recent metaanalysis of available genome scans showed no regions with a conclusive evidence of linkage. 20 The relatively slow progress of gene-mapping efforts is often explained by the 'complex' nature of the illness and of the genotype-phenotype relation. The complexity most likely includes heterogeneity, interactions of multiple loci, incomplete penetrance, as well as phenotypes resulting from environmental effects-either alone or in interaction with the genetic predisposition. The goal of psychiatric genetic research is identification of (heritable) variations in DNA sequence or function that influence behaviour or give rise to mental illness. By definition, in complex (multifactorial) traits, this link is not unique and specific. That is, a particular change in gene sequence does not necessarily lead to a specific behaviour, and similar behaviours (symptoms) may be due to distinct (sets of) genes. Moreover, we must consider the possibility that the path between the genotype and behaviour is not unidirectional. Emerging examples point not only to general effects of environment, for instance stress, on behaviour, but also to specific behaviours influencing gene function that can be transmitted onto the next generation. 21 No single method is considered clearly superior in identifying susceptibility genes for complex traits such as BD. Most researchers agree that a combination of strategies is most lik...

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“…found evidence linking psychotic symptoms in bipolar patients with 13q31 and 22q12 but not 10p12-14 or 18p11.2, all regions where bipolar and schizophrenia susceptibility overlap. The region 18q21-23 appears associated particularly with milder bipolar disorder, suggesting perhaps that bipolar II forms a valid subtype (McMahon et al 2001). Faraone et al (2004) have tentatively identified three new chromosomal regions associated with age of onset in bipolar disorder.…”

Section: The Role Of Genetic Factorsmentioning

confidence: 99%

Recent findings in bipolar affective disorder

Bebbington¹

2004

Psychol. Med.

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Goodwin (2000) famously argued that bipolar disorder was the Cinderella of psychiatry. It certainly should not be: there is no doubt of the anguish caused by the condition, in particular the excess of natural mortality and the great excess of death by suicide (Ösby et al. 2001). In this issue, Mitchell et al. (2004) report that 26% of their cases of bipolar disorder had attempted suicide at some point. This reflects the sheer persistence of personal suffering: Judd and colleagues (2002, 2003) demonstrated in a long and detailed follow-up that patients with bipolar disorder were symptomatic at least half the time. The Australian National Survey of Psychotic Disorders found levels of disability in affective psychosis equal to those of schizophrenia (Jablensky et al. 2000), and bipolar cases are more likely to score highly on measures of disability than unipolar cases (Mitchell et al. 2004). People with bipolar disorder are more likely to be single, widowed or divorced than both the general populace and those with unipolar depression (Mitchell et al. 2004).

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Linkage of Bipolar Disorder to Chromosome 18q and the Validity of Bipolar II Disorder

Cited by 95 publications

References 31 publications

Genome-wide scan of bipolar disorder in 65 pedigrees: supportive evidence for linkage at 8q24, 18q22, 4q32, 2p12, and 13q12

Genome-wide scan of bipolar disorder in 65 pedigrees: supportive evidence for linkage at 8q24, 18q22, 4q32, 2p12, and 13q12

The phenotypes of bipolar disorder: relevance for genetic investigations

Recent findings in bipolar affective disorder

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