Evidence for Linkage of Bipolar Disorder to Chromosome 18 with a Parent-of-Origin Effect (original) (raw)
- Journal List
- Am J Hum Genet
- v.57(6); 1995 Dec
- PMC1801428
Am J Hum Genet. 1995 Dec; 57(6): 1384–1394.
O. Colin Stine, Jianfeng Xu, Rebecca Koskela, Francis J. McMahon, Michele Gschwend, Carl Friddle, Chris D. Clark, Melvin G. McInnis, 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, and J. Raymond DePaulo
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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- Baron M. Linkage between an X-chromosome marker (deutan color blindness) and bipolar affective illness. Occurrence in the family of a lithium carbonate-responsive schizo-affective proband. Arch Gen Psychiatry. 1977 Jun;34(6):721–725. [PubMed] [Google Scholar]
- Baron M, Freimer NF, Risch N, Lerer B, Alexander JR, Straub RE, Asokan S, Das K, Peterson A, Amos J, et al. Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees. Nat Genet. 1993 Jan;3(1):49–55. [PubMed] [Google Scholar]
- Berrettini WH, Ferraro TN, Goldin LR, Weeks DE, Detera-Wadleigh S, Nurnberger JI, Jr, Gershon ES. Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5918–5921. [PMC free article] [PubMed] [Google Scholar]
- Coryell W, Endicott J, Andreasen N, Keller M. Bipolar I, bipolar II, and nonbipolar major depression among the relatives of affectively ill probands. Am J Psychiatry. 1985 Jul;142(7):817–821. [PubMed] [Google Scholar]
- Crowe RR, Smouse PE. The genetic implications of age-dependent penetrance in manic-depressive illness. J Psychiatr Res. 1977;13(4):273–285. [PubMed] [Google Scholar]
- Easton DF, Bishop DT, Ford D, Crockford GP. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1993 Apr;52(4):678–701. [PMC free article] [PubMed] [Google Scholar]
- Egeland JA, Gerhard DS, Pauls DL, Sussex JN, Kidd KK, Allen CR, Hostetter AM, Housman DE. Bipolar affective disorders linked to DNA markers on chromosome 11. Nature. 325(6107):783–787. [PubMed] [Google Scholar]
- Endicott J, Nee J, Andreasen N, Clayton P, Keller M, Coryell W. Bipolar II. Combine or keep separate? J Affect Disord. 1985 Jan-Feb;8(1):17–28. [PubMed] [Google Scholar]
- Endicott J, Spitzer RL. A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry. 1978 Jul;35(7):837–844. [PubMed] [Google Scholar]
- Gantz I, Tashiro T, Barcroft C, Konda Y, Shimoto Y, Miwa H, Glover T, Munzert G, Yamada T. Localization of the genes encoding the melanocortin-2 (adrenocorticotropic hormone) and melanocortin-3 receptors to chromosomes 18p11.2 and 20q13.2-q13.3 by fluorescence in situ hybridization. Genomics. 1993 Oct;18(1):166–167. [PubMed] [Google Scholar]
- Gershon ES, Targum SD, Matthysse S, Bunney WE., Jr Color blindness not closely linked to bipolar illness. Report of a new pedigree series. Arch Gen Psychiatry. 1979 Dec;36(13):1423–1430. [PubMed] [Google Scholar]
- Goldin LR, Gershon ES, Targum SD, Sparkes RS, McGinniss M. Segregation and linkage analyses in families of patients with bipolar, unipolar, and schizoaffective mood disorders. Am J Hum Genet. 1983 Mar;35(2):274–287. [PMC free article] [PubMed] [Google Scholar]
- Gyapay G, Morissette J, Vignal A, Dib C, Fizames C, Millasseau P, Marc S, Bernardi G, Lathrop M, Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. [PubMed] [Google Scholar]
- Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, King MC. Linkage of early-onset familial breast cancer to chromosome 17q21. Science. 1990 Dec 21;250(4988):1684–1689. [PubMed] [Google Scholar]
- Jones DT, Reed RR. Golf: an olfactory neuron specific-G protein involved in odorant signal transduction. Science. 1989 May 19;244(4906):790–795. [PubMed] [Google Scholar]
- Kelsoe JR, Ginns EI, Egeland JA, Gerhard DS, Goldstein AM, Bale SJ, Pauls DL, Long RT, Kidd KK, Conte G, et al. Re-evaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish. Nature. 1989 Nov 16;342(6247):238–243. [PubMed] [Google Scholar]
- Kruglyak L, Lander ES. High-resolution genetic mapping of complex traits. Am J Hum Genet. 1995 May;56(5):1212–1223. [PMC free article] [PubMed] [Google Scholar]
- Lander ES, Green P. Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2363–2367. [PMC free article] [PubMed] [Google Scholar]
- Lander ES, Schork NJ. Genetic dissection of complex traits. Science. 1994 Sep 30;265(5181):2037–2048. [PubMed] [Google Scholar]
- Lathrop GM, Lalouel JM, Julier C, Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. [PMC free article] [PubMed] [Google Scholar]
- McInnis MG, McMahon FJ, Chase GA, Simpson SG, Ross CA, DePaulo JR., Jr Anticipation in bipolar affective disorder. Am J Hum Genet. 1993 Aug;53(2):385–390. [PMC free article] [PubMed] [Google Scholar]
- McMahon FJ, Stine OC, Chase GA, Meyers DA, Simpson SG, DePaulo JR., Jr Influence of clinical subtype, sex, and lineality on age at onset of major affective disorder in a family sample. Am J Psychiatry. 1994 Feb;151(2):210–215. [PubMed] [Google Scholar]
- McMahon FJ, Stine OC, Meyers DA, Simpson SG, DePaulo JR. Patterns of maternal transmission in bipolar affective disorder. Am J Hum Genet. 1995 Jun;56(6):1277–1286. [PMC free article] [PubMed] [Google Scholar]
- Mendlewicz J, Fleiss JL, Fieve RR. Evidence for X-linkage in the transmission of manic-depressive illness. JAMA. 1972 Dec 25;222(13):1624–1627. [PubMed] [Google Scholar]
- Mendlewicz J, Rainer JD. Morbidity risk and genetic transmission in manic-depressive illness. Am J Hum Genet. 1974 Nov;26(6):692–701. [PMC free article] [PubMed] [Google Scholar]
- MORTON NE. The detection and estimation of linkage between the genes for elliptocytosis and the Rh blood type. Am J Hum Genet. 1956 Jun;8(2):80–96. [PMC free article] [PubMed] [Google Scholar]
- O'Rourke DH, McGuffin P, Reich T. Genetic analysis of manic-depressive illness. Am J Phys Anthropol. 1983 Sep;62(1):51–59. [PubMed] [Google Scholar]
- Reich T, Clayton PJ, Winokur G. Family history studies: V. The genetics of mania. Am J Psychiatry. 1969 Apr;125(10):1358–1369. [PubMed] [Google Scholar]
- Rice J, Reich T, Andreasen NC, Endicott J, Van Eerdewegh M, Fishman R, Hirschfeld RM, Klerman GL. The familial transmission of bipolar illness. Arch Gen Psychiatry. 1987 May;44(5):441–447. [PubMed] [Google Scholar]
- Robins LN, Helzer JE, Weissman MM, Orvaschel H, Gruenberg E, Burke JD, Jr, Regier DA. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry. 1984 Oct;41(10):949–958. [PubMed] [Google Scholar]
- Schalling M, Hudson TJ, Buetow KH, Housman DE. Direct detection of novel expanded trinucleotide repeats in the human genome. Nat Genet. 1993 Jun;4(2):135–139. [PubMed] [Google Scholar]
- Simpson SG, Folstein SE, Meyers DA, DePaulo JR. Assessment of lineality in bipolar I linkage studies. Am J Psychiatry. 1992 Dec;149(12):1660–1665. [PubMed] [Google Scholar]
- Straub RE, Speer MC, Luo Y, Rojas K, Overhauser J, Ott J, Gilliam TC. A microsatellite genetic linkage map of human chromosome 18. Genomics. 1993 Jan;15(1):48–56. [PubMed] [Google Scholar]
- Suarez BK, Van Eerdewegh P. A comparison of three affected-sib-pair scoring methods to detect HLA-linked disease susceptibility genes. Am J Med Genet. 1984 May;18(1):135–146. [PubMed] [Google Scholar]
- Terwilliger JD. A powerful likelihood method for the analysis of linkage disequilibrium between trait loci and one or more polymorphic marker loci. Am J Hum Genet. 1995 Mar;56(3):777–787. [PMC free article] [PubMed] [Google Scholar]
- Terwilliger JD, Ott J. A novel polylocus method for linkage analysis using the lod-score or affected sib-pair method. Genet Epidemiol. 1993;10(6):477–482. [PubMed] [Google Scholar]
- Walsh FS, Barton CH, Putt W, Moore SE, Kelsell D, Spurr N, Goodfellow PN. N-cadherin gene maps to human chromosome 18 and is not linked to the E-cadherin gene. J Neurochem. 1990 Sep;55(3):805–812. [PubMed] [Google Scholar]
- Weeks DE, Lehner T, Squires-Wheeler E, Kaufmann C, Ott J. Measuring the inflation of the lod score due to its maximization over model parameter values in human linkage analysis. Genet Epidemiol. 1990;7(4):237–243. [PubMed] [Google Scholar]
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