Evidence for linkage of bipolar disorder to HC 18 with a parent-of-origin effect

Stine, O. Colin; Xu, Jianfeng; Koskela, Rebecca; McMahon, Francis J.; Gschwend, Michele; Friddle, Carl; Clark, Caroline; McInnis, Melvin G.; Simpson, Sylvia G.; Breschel, Theresa S.; Vishio, E.; Riskin, K; Feilotter, Harriet; Chen, E.; Shen, Sa; Folstein, Susan E.; Meyers, Deborah A.; Botstein, David; Marr, Thomas G.; DePaulo, J. Raymond

doi:10.1016/0006-3223(96)84084-4

Cited by 192 publications

(345 citation statements)

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“…50,51 However, some of these findings were not replicated. 52 On the other hand, linkage of bipolar disorder with chromosome 18 (18q22 and 18p11) was observed only in the paternal transmission, 53 which was replicated in several studies. 54 POE was also reported in other chromosomes such as 6q, 55 13q12, and 1q41.…”

Section: Mitochondrial Dna (Mtdna) Heteroplasmymentioning

confidence: 72%

Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders

et al. 2005

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Classical twin research focused on differentiating genetic factors from environmental factors by comparing the concordance rate between monozygotic (MZ) and dizygotic twins. On the other hand, recent twin research tries to identify genetic or epigenetic differences between MZ twins discordant for mental disorders. There are a number of reports of MZ twins discordant for genetic disorders caused by genetic or epigenetic differences of known pathogenic genes. In the case of mental disorder research, for which the causative gene has not been established yet, we are trying to identify the 'pathogenic gene' by comprehensive analysis of genetic or epigenetic difference between discordant MZ twins. To date, no compelling evidence suggesting such difference between MZ twins has been reported. However, if the genetic or epigenetic difference responsible for the discordant phenotype is found, it will have impact on the biology of mental disorder, in which few conclusive molecular genetic evidences have been obtained.

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Section: Mitochondrial Dna (Mtdna) Heteroplasmymentioning

confidence: 72%

Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders

et al. 2005

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“…144 However, differences in prevalence between men and women are well established in BDII, and some studies find preferential transmission from mother compared to father as well as parent-of-origin effects in linkage data, especially data on chromosome 18. 15,145 Moreover, several intriguing findings with respect to mitochondrial mechanisms have been published, some of them linking these with the chromosome 18p results. 146,147 Anticipation refers to the phenomenon of increased severity and/or earlier age at onset in successive generations.…”

Section: Response To Long-term Treatmentmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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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“…8,9 Two genes encoding human IMPases have been identified: IMPA1 and IMPA2. IMPA2 was proposed as a plausible candidate gene by Yoshikawa et al, 10 because of its location within a region of positive linkage findings to BP 14,15 and the possible functional role of the inositol phospholipid signalling system. Yoshikawa et al 16 reported that the group of haplotypes containing either À185A, 97-15G or 558C have significantly higher frequencies in schizophrenics, but not in bipolar disorder patients from Japan.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 The gene is a potential biochemical target for the action of lithium. 13 Linkage studies 14,15 have suggested the presence of a susceptibility locus for bipolar disorder on chromosome 18p11.2. The gene has been screened for polymorphisms and tested for association with BP 11,12 and schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Association study of myo-inositol monophosphatase 2 (IMPA2) polymorphisms with bipolar affective disorder and response to lithium treatment

et al. 2004

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Lithium is the most effective mood-stabilizing drug in the therapy of bipolar affective disorder (BP). It is thought to exert its effect via the phosphatidylinositol signalling system. Myo-inositol monophosphatase 2 (IMPA2) codes for an enzyme in this system that is inhibited by lithium. It is located on 18p11.2, a region implicated as a BP susceptibility locus. We examined eight single-nucleotide polymorphisms (SNPs) identified within this gene for association with BP, using 237 parents-offspring trios and in 174 cases and 170 controls. No SNP showed association with BP. When good responders to lithium treatment were compared with the poor responders, some statistically significant differences emerged for two SNPs; however, the sample became too small to draw definitive conclusions. We cannot find support for the involvement of variation in IMPA2 in susceptibility to bipolar disorder, but the role of this and other genes from the phosphoinositol signalling pathway in predicting response to lithium treatment merits further investigation.

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Evidence for linkage of bipolar disorder to HC 18 with a parent-of-origin effect

Cited by 192 publications

References 0 publications

Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders

Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders

The phenotypes of bipolar disorder: relevance for genetic investigations

Association study of myo-inositol monophosphatase 2 (IMPA2) polymorphisms with bipolar affective disorder and response to lithium treatment

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