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

O. Colin Stine, Jianfeng Xu, Rebecca Koskela, Francis J. McMahon, Michele Gschwend, Carl Friddle, Chris D. Clark, Melvin G. Mclnnis, Sylvia G. Simpson, Theresa S. Breschel, Eva Vishio, Kelly Riskin, Harriet Feilotter, Eugene Chen, Susan Shen, Susan Folstein, Deborah A. Meyers, David Botstein, Thomas G. Marr, J. Raymond DePaulo

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Abstract

A susceptibility gene on chromosome 18 and a parent-of-origin effect have been suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear families selected for apparent unilineal transmission of the BPAD phenotype, by using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was tested with affected-sib-pair and LOD score methods under two definitions of the affected phenotype. The affected-sib-pair analyses indicated excess allele sharing for markers on 18p within the region reported previously. The greatest sharing was at D18S37: 64% in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006). In addition, excess sharing of the paternally, but not maternally, transmitted alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib pairs were concordant for paternally transmitted alleles, and 21 pairs were discordant (P = .0004). The evidence for linkage to loci on both 18p and 18q was strongest in the 11 paternal pedigrees, i.e., those in which the father or one of the father's sibs is affected. In these pedigrees, the greatest allele sharing (81%; P = .00002) and the highest LOD score (3.51; θ = 0.0) were observed at D18S41. Our results provide further support for linkage of BPAD to chromosome 18 and the first molecular evidence for a parent-of-origin effect operating in this disorder. The number of loci involved, and their precise location, require further study.

Original languageEnglish
Pages (from-to)1384-1394
Number of pages11
JournalAmerican Journal of Human Genetics
Volume57
Issue number6
StatePublished - Dec 1 1995

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Chromosomes, Human, Pair 18
Bipolar Disorder
Mood Disorders
Alleles
Pedigree
Fathers
Phenotype
Nuclear Family
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Stine, O. C., Xu, J., Koskela, R., McMahon, F. J., Gschwend, M., Friddle, C., ... DePaulo, J. R. (1995). Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect. American Journal of Human Genetics, 57(6), 1384-1394.

Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect. / Stine, O. Colin; Xu, Jianfeng; Koskela, Rebecca; McMahon, Francis J.; Gschwend, Michele; Friddle, Carl; Clark, Chris D.; Mclnnis, Melvin G.; Simpson, Sylvia G.; Breschel, Theresa S.; Vishio, Eva; Riskin, Kelly; Feilotter, Harriet; Chen, Eugene; Shen, Susan; Folstein, Susan; Meyers, Deborah A.; Botstein, David; Marr, Thomas G.; DePaulo, J. Raymond.

In: American Journal of Human Genetics, Vol. 57, No. 6, 01.12.1995, p. 1384-1394.

Research output: Contribution to journalArticle

Stine, OC, Xu, J, Koskela, R, McMahon, FJ, Gschwend, M, Friddle, C, Clark, CD, Mclnnis, MG, Simpson, SG, Breschel, TS, Vishio, E, Riskin, K, Feilotter, H, Chen, E, Shen, S, Folstein, S, Meyers, DA, Botstein, D, Marr, TG & DePaulo, JR 1995, 'Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect', American Journal of Human Genetics, vol. 57, no. 6, pp. 1384-1394.
Stine OC, Xu J, Koskela R, McMahon FJ, Gschwend M, Friddle C et al. Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect. American Journal of Human Genetics. 1995 Dec 1;57(6):1384-1394.
Stine, O. Colin ; Xu, Jianfeng ; Koskela, Rebecca ; McMahon, Francis J. ; Gschwend, Michele ; Friddle, Carl ; Clark, Chris D. ; Mclnnis, Melvin G. ; Simpson, Sylvia G. ; Breschel, Theresa S. ; Vishio, Eva ; Riskin, Kelly ; Feilotter, Harriet ; Chen, Eugene ; Shen, Susan ; Folstein, Susan ; Meyers, Deborah A. ; Botstein, David ; Marr, Thomas G. ; DePaulo, J. Raymond. / Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect. In: American Journal of Human Genetics. 1995 ; Vol. 57, No. 6. pp. 1384-1394.
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abstract = "A susceptibility gene on chromosome 18 and a parent-of-origin effect have been suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear families selected for apparent unilineal transmission of the BPAD phenotype, by using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was tested with affected-sib-pair and LOD score methods under two definitions of the affected phenotype. The affected-sib-pair analyses indicated excess allele sharing for markers on 18p within the region reported previously. The greatest sharing was at D18S37: 64{\%} in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006). In addition, excess sharing of the paternally, but not maternally, transmitted alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib pairs were concordant for paternally transmitted alleles, and 21 pairs were discordant (P = .0004). The evidence for linkage to loci on both 18p and 18q was strongest in the 11 paternal pedigrees, i.e., those in which the father or one of the father's sibs is affected. In these pedigrees, the greatest allele sharing (81{\%}; P = .00002) and the highest LOD score (3.51; θ = 0.0) were observed at D18S41. Our results provide further support for linkage of BPAD to chromosome 18 and the first molecular evidence for a parent-of-origin effect operating in this disorder. The number of loci involved, and their precise location, require further study.",
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T1 - Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect

AU - Stine, O. Colin

AU - Xu, Jianfeng

AU - Koskela, Rebecca

AU - McMahon, Francis J.

AU - Gschwend, Michele

AU - Friddle, Carl

AU - Clark, Chris D.

AU - Mclnnis, Melvin G.

AU - Simpson, Sylvia G.

AU - Breschel, Theresa S.

AU - Vishio, Eva

AU - Riskin, Kelly

AU - Feilotter, Harriet

AU - Chen, Eugene

AU - Shen, Susan

AU - Folstein, Susan

AU - Meyers, Deborah A.

AU - Botstein, David

AU - Marr, Thomas G.

AU - DePaulo, J. Raymond

PY - 1995/12/1

Y1 - 1995/12/1

N2 - A susceptibility gene on chromosome 18 and a parent-of-origin effect have been suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear families selected for apparent unilineal transmission of the BPAD phenotype, by using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was tested with affected-sib-pair and LOD score methods under two definitions of the affected phenotype. The affected-sib-pair analyses indicated excess allele sharing for markers on 18p within the region reported previously. The greatest sharing was at D18S37: 64% in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006). In addition, excess sharing of the paternally, but not maternally, transmitted alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib pairs were concordant for paternally transmitted alleles, and 21 pairs were discordant (P = .0004). The evidence for linkage to loci on both 18p and 18q was strongest in the 11 paternal pedigrees, i.e., those in which the father or one of the father's sibs is affected. In these pedigrees, the greatest allele sharing (81%; P = .00002) and the highest LOD score (3.51; θ = 0.0) were observed at D18S41. Our results provide further support for linkage of BPAD to chromosome 18 and the first molecular evidence for a parent-of-origin effect operating in this disorder. The number of loci involved, and their precise location, require further study.

AB - A susceptibility gene on chromosome 18 and a parent-of-origin effect have been suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear families selected for apparent unilineal transmission of the BPAD phenotype, by using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was tested with affected-sib-pair and LOD score methods under two definitions of the affected phenotype. The affected-sib-pair analyses indicated excess allele sharing for markers on 18p within the region reported previously. The greatest sharing was at D18S37: 64% in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006). In addition, excess sharing of the paternally, but not maternally, transmitted alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib pairs were concordant for paternally transmitted alleles, and 21 pairs were discordant (P = .0004). The evidence for linkage to loci on both 18p and 18q was strongest in the 11 paternal pedigrees, i.e., those in which the father or one of the father's sibs is affected. In these pedigrees, the greatest allele sharing (81%; P = .00002) and the highest LOD score (3.51; θ = 0.0) were observed at D18S41. Our results provide further support for linkage of BPAD to chromosome 18 and the first molecular evidence for a parent-of-origin effect operating in this disorder. The number of loci involved, and their precise location, require further study.

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