A Linkage Study of Bipolar Illness

Berrettini, Wade H.; Ferraro, Thomas N.; Goldin, Lynn R.; Detera‐Wadleigh, Sevilla D.; Choi, Henry; Muniec, David; Guroff, Juliet J.; Kazuba, Diane; Nürnberger, John I.; Hsieh, Wang-Ting; Hoehe, Margret R.; Gershon, Elliot S.

doi:10.1001/archpsyc.1997.01830130031006

Cited by 106 publications

(78 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, positive findings were obtained after subdividing the families according to the gender of the disease-transmitting parent. Our linkage data support the modest evidence for linkage with markers on 18p11.2 originally reported by Berrettini et al 2,20 In accordance with the results of Stine et al 3 and Gershon et al 4 we found the highest LOD scores in the subset of paternal families. Moreover, our multipoint LOD score peaked at the same loci (D18S37, D18S453, D18S40; Figure 1) where Gershon et al 4 and Stine et al 3 found their highest LOD scores on 18p11.2.…”

Section: Affected-sib-pair Analysissupporting

confidence: 93%

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

et al. 1999

View full text Add to dashboard Cite

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...

show abstract

Section: Affected-sib-pair Analysissupporting

confidence: 93%

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

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Several regions on chromosome 18 have been implied [15][16][17][18][19][20][21][22][23] and reviewed by Potash and Depaulo Jr. 73 We have previously reported a lod score of 1.83 at D18S67 in family 4. 41 We did not find much support for this region with non-parametric 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

View full text Add to dashboard Cite

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.

show abstract

“…[21][22][23][24][25] Low positive lod scores less than 1 have been reported by Sherrington et al 18 23 reported a lod score of 0.76 at 0.11 recombination fraction for D4S394 in one of their two Costa Rican families and of 1.06 at 0.07 recombination fraction at nearby marker D4S171 in the other Costa Rican family. As part of the NIMH genome scan, Detera-Wadleigh et al 26 did not find evidence of increased allele sharing at or near D4S394.…”

mentioning

confidence: 85%

Support for the possible locus on chromosome 4p16 for bipolar affective disorder

Ewald¹,

Degn²,

Mors³

et al. 1998

Mol Psychiatry

View full text Add to dashboard Cite

Significant evidence for linkage between bipolar affective disorder and markers on chromosome 4p16 has been reported in Scottish families. 1 Linkage analyses using 16 DNA markers covering more than 50 cM from chromosome 4pter-4p12, including candidate genes encoding the dopamine D5 receptor and an adrenergic receptor (2C), were performed in two Danish families 2,3 with bipolar affective disorder. Assuming homogeneity in the two families, the highest lod score found in the two-point linkage analyses was 2.00 at 0.03 recombination fraction for D4S394, ie the marker which also was most significant in the original Scottish study. Simulation showed that such a lod score would only occur six out of 10 000 times with an unlinked marker. Though the present study thus replicates the Scottish findings according to the criteria suggested by Lander and Kruglyak, 4 caution is warranted as the mode of inheritance which yielded the highest lod score in the two studies was different. Final proof of a disease locus in the Scottish and our study has to await the identification of a DNA sequence of functional significance for bipolar disorder.

show abstract

A Linkage Study of Bipolar Illness

Abstract: Our results imply that a BP susceptibility gene exists near the centromere of chromosome 18. Confirmation of this finding (by independent investigators studying different pedigrees) has been published, suggesting that a valid BP disease linkage may have been discovered.

Cited by 106 publications

References 45 publications

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

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

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

Support for the possible locus on chromosome 4p16 for bipolar affective disorder

Contact Info

Product

Resources

About