BACKGROUND: We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for: 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p. METHODS: Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6. Nonparametric linkage analysis was performed. RESULTS: Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p =.006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6p22.2 (r =.26; p <.0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p <.0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from.35 to 2.26 on 6p22.2. CONCLUSIONS: These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia.
BACKGROUND: We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for: 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p. METHODS: Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6. Nonparametric linkage analysis was performed. RESULTS: Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p =.006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6p22.2 (r =.26; p <.0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p <.0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from.35 to 2.26 on 6p22.2. CONCLUSIONS: These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia.
Authors: Matthew B McQueen; B Devlin; Stephen V Faraone; Vishwajit L Nimgaonkar; Pamela Sklar; Jordan W Smoller; Rami Abou Jamra; Margot Albus; Silviu-Alin Bacanu; Miron Baron; Thomas B Barrett; Wade Berrettini; Deborah Blacker; William Byerley; Sven Cichon; Willam Coryell; Nick Craddock; Mark J Daly; J Raymond Depaulo; Howard J Edenberg; Tatiana Foroud; Michael Gill; T Conrad Gilliam; Marian Hamshere; Ian Jones; Lisa Jones; Suh-Hang Juo; John R Kelsoe; David Lambert; Christoph Lange; Bernard Lerer; Jianjun Liu; Wolfgang Maier; James D Mackinnon; Melvin G McInnis; Francis J McMahon; Dennis L Murphy; Markus M Nothen; John I Nurnberger; Carlos N Pato; Michele T Pato; James B Potash; Peter Propping; Ann E Pulver; John P Rice; Marcella Rietschel; William Scheftner; Johannes Schumacher; Ricardo Segurado; Kristel Van Steen; Weiting Xie; Peter P Zandi; Nan M Laird Journal: Am J Hum Genet Date: 2005-08-15 Impact factor: 11.025
Authors: Johannes Schumacher; Radka Kaneva; Rami Abou Jamra; Guillermo Orozco Diaz; Stephanie Ohlraun; Vihra Milanova; Young-Ae Lee; Fabio Rivas; Fermin Mayoral; Robert Fuerst; Antonia Flaquer; Christine Windemuth; Eudoxia Gay; Sebastian Sanz; Maria José González; Susana Gil; Francisco Cabaleiro; Francisco del Rio; Fermin Perez; Jesus Haro; Christian Kostov; Vesselin Chorbov; Amelia Nikolova-Hill; Vessela Stoyanova; George Onchev; Ivo Kremensky; Konstantin Strauch; Thomas G Schulze; Peter Nürnberg; Wolfgang Gaebel; Ansgar Klimke; Georg Auburger; Thomas F Wienker; Luba Kalaydjieva; Peter Propping; Sven Cichon; Assen Jablensky; Marcella Rietschel; Markus M Nöthen Journal: Am J Hum Genet Date: 2005-11-02 Impact factor: 11.025
Authors: W Tang; Y Shi; G Feng; L Yan; Y Xing; S Zhu; J Liu; X Zhao; R Tang; J Du; J Zhang; G He; P Liang; L He Journal: J Neural Transm (Vienna) Date: 2006-02-09 Impact factor: 3.575
Authors: Rami Abou Jamra; Robert Fuerst; Radka Kaneva; Guillermo Orozco Diaz; Fabio Rivas; Fermin Mayoral; Eudoxia Gay; Sebastian Sans; Maria Jose Gonzalez; Susana Gil; Francisco Cabaleiro; Francisco Del Rio; Fermin Perez; Jesus Haro; Georg Auburger; Vihra Milanova; Christian Kostov; Vesselin Chorbov; Vessela Stoyanova; Amelia Nikolova-Hill; George Onchev; Ivo Kremensky; Assen Jablensky; Thomas G Schulze; Peter Propping; Marcella Rietschel; Markus M Nothen; Sven Cichon; Thomas F Wienker; Johannes Schumacher Journal: Am J Hum Genet Date: 2007-09-17 Impact factor: 11.025
Authors: G Shaltiel; S Maeng; O Malkesman; B Pearson; R J Schloesser; T Tragon; M Rogawski; M Gasior; D Luckenbaugh; G Chen; H K Manji Journal: Mol Psychiatry Date: 2008-03-11 Impact factor: 15.992