Linkage studies of bipolar disorder in the region of the Darier's disease gene on chromosome 12q23‐24.1

Dawson, Elisabeth; Parfitt, E.; Roberts, Queta; Daniels, J.; Lim, Lionel; Sham, Pak C.; Nöthen, Markus M.; Propping, Peter; Lanczik, M.; Maier, Wolfgang; Reuner, Ulrike; Weissenbach, Jean; Gill, Michael; Powell, John; McGuffin, Peter; Owen, Mike; Craddock, Nick

doi:10.1002/ajmg.1320600203

Cited by 106 publications

(74 citation statements)

References 33 publications

(8 reference statements)

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“…A number of other studies have since reported linkage of BP and recurrent major depression to this region. [24][25][26][27][28][29][30] However, no susceptibility gene for these disorders has yet been identified in this region.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide linkage scan of 98 bipolar pedigrees and analysis of clinical covariates

et al. 2007

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Despite compelling evidence that genetic factors contribute to bipolar disorder (BP), attempts to identify susceptibility genes have met with limited success. This may be due to the genetic heterogeneity of the disorder. We sought to identify susceptibility loci for BP in a genome-wide linkage scan with and without clinical covariates that might reflect the underlying heterogeneity of the disorder. We genotyped 428 subjects in 98 BP families at the Center for Inherited Disease Research with 402 microsatellite markers. We first carried out a nonparametric linkage analysis with MERLIN, and then reanalyzed the data with LODPAL to incorporate clinical covariates for age at onset (AAO), psychosis and comorbid anxiety. We sought to further examine the top findings in the covariate analysis in an independent sample of 64 previously collected BP families. In the non-parametric linkage analysis, three loci were nominally significant under a narrow diagnostic model and seven other loci were nominally significant under a broader model. The top findings were on chromosomes 2q24 and 3q28. The covariate analyses yielded additional evidence for linkage on 3q28 with AAO in the primary and independent samples. Although none of the linked loci were genome-wide significant, their congruence with prior results and, for the covariate analyses, their identification in two separate samples increases the likelihood that they are true positives and deserve further investigation. These findings further demonstrate the value of considering clinical features that may reflect the underlying heterogeneity of disease in order to facilitate gene mapping.

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Section: Discussionmentioning

confidence: 99%

Genome-wide linkage scan of 98 bipolar pedigrees and analysis of clinical covariates

et al. 2007

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“…11 In addition, a more proximal region including the distal part of chromosome 12q23 has been suggested. 9,62 The locus suggested on chromosome 1p22-p21 close to D1S216 at 104 cM from the p-telomere yielded the highest affecteds-only lod score of 2.75 (genome-wide P-value 0.1622). Two-point lod scores at other nearby markers supported the finding ( Figure 2 and Table 1) and the lod score increased to 2.98 (genome-wide Pvalue 0.1022) when performing three-point analyses.…”

Section: Discussionmentioning

confidence: 99%

A genome-wide scan shows significant linkage between bipolar disorder and chromosome 12q24.3 and suggestive linkage to chromosomes 1p22–21, 4p16, 6q14–22, 10q26 and 16p13.3

Ewald¹,

Flint²,

Kruse

et al. 2002

Mol Psychiatry

127

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The present study reports a genomewide scan using linkage analysis for risk genes involved in bipolar disorder with 613 microsatellite markers including additional testing of promising regions. As previously published significant linkage was obtained at chromosome 12q24.3 with a two-point parametric lod score of 3.42 at D12S1639 including all members in both families (empirical P-value 0.00004, genome-wide P-value 0.0417). The multipoint parametric lod score at D12S1639 was 3.63 (genome-wide P-value 0.0265). At chromosome 1p22-p21 a parametric, affecteds-only two-point lod score of 2.75 at marker D1S216 was found (empirical Pvalue 0.0002, genome-wide P-value 0.1622). A three-point lod score of 2.98 (genome-wide Pvalue 0.1022) at D1S216, and a multipoint non-parametric analysis with a maximum NPL-all score of 17.60 (P-value 0.00079) at D1S216 further supported this finding. A number of additional loci on chromosomes 4p16, 6q14-q22, 10q26 and 16p13.3 yielded parametric lod scores around or above 2.

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“…Results from a subsample of the present sample have previously been published for markers on chromosome 12. 31 The mean number of individuals per pedigree was 6.8. The distribution of diagnoses was as follows: 103 individuals with BPI, 26 individuals with BPII, nine individuals with SA/BP, 38 individuals with UPR, and 38 individuals with a minor psychiatric diagnosis.…”

Section: Description Of Familiesmentioning

confidence: 99%

Evaluation of linkage of bipolar affective disorder to chromosome 18 in a sample of 57 German families

et al. 1999

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Previously reported linkage of bipolar affective disorder to DNA markers on chromosome 18 was reexamined in a large sample of German bipolar families. Twenty-three short tandem repeat markers were investigated in 57 families containing 103 individuals with bipolar I disorder (BPI), 26 with bipolar II disorder (BPII), nine with schizoaffective disorder of the bipolar type (SA/BP), and 38 individuals with recurrent unipolar depression (UPR). Evidence for linkage was tested with parametric and non-parametric methods under two definitions of the affected phenotype. Analysis of all 57 families revealed no robust evidence for linkage. Following previous reports we performed separate analyses after subdividing the families with respect to the sex of the transmitting parent. Fourteen families were classified as paternal and 12 families as maternal. In 31 families the parental lineage of transmission of the disease could not be determined ('either' families). Evidence for linkage was obtained for chromosomal region 18p11.2 in the paternal families and for 18q22-23 in the 'either' families. The findings on 18p11.2 and 18q22-23 support prior evidence for susceptibility loci in these regions. The parent-of-origin effect on 18p11.2 is confirmed in our sample. The delineation of characteristics of 'either' families requires further study.Although the etiology of bipolar affective disorder is unknown, strong support for an important genetic component comes from the results of family, twin, and adoption studies. 1 Linkage studies of bipolar disorder to date have provided suggestive evidence in favor of locus heterogeneity. Promising chromosomal regions suggested by recent linkage studies include regions on chromosome 18.Berrettini et al 2 first reported linkage of bipolar disorder to a region near the centromere on chromosome 18p in 22 families using the affected-sib-pair (ASP) method and the affected-pedigree-member (APM) method. Parametric LOD score analysis of all 22 families revealed negative LOD scores. However, individual families yielded LOD scores Ͼ1 assuming dominant or recessive genetic models. Confirmatory evidence for a bipolar susceptibility locus in this chromosomal region was found by Stine et al. 3 Both parametric LOD score analysis and ASP analysis supported linkage in their study of 28 families. In addition, the same study reported a second susceptibility locus on the long arm of chromosome 18 (18q21). Interestingly, linkage to loci on both 18p and 18q was strongest in those families, in which the father or one of the father's siblings was affected, suggesting a parent-of-origin effect operating in bipolar disorder. Gershon et al 4 re-analyzed the 18p marker data of Berrettini et al 2 by the sex of the transmitting parent. Although no kindred with limited paternal transmission was observed, ASP analysis yielded highly significant excess allele sharing in the pedigrees with mixed maternal-paternal transmission (in different pedigree branches) but not in pedigrees with exclusively maternal transmission confirmin...

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Linkage studies of bipolar disorder in the region of the Darier's disease gene on chromosome 12q23‐24.1

Cited by 106 publications

References 33 publications

Genome-wide linkage scan of 98 bipolar pedigrees and analysis of clinical covariates

Genome-wide linkage scan of 98 bipolar pedigrees and analysis of clinical covariates

A genome-wide scan shows significant linkage between bipolar disorder and chromosome 12q24.3 and suggestive linkage to chromosomes 1p22–21, 4p16, 6q14–22, 10q26 and 16p13.3

Evaluation of linkage of bipolar affective disorder to chromosome 18 in a sample of 57 German families

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