OBJECTIVE: Linkage studies of bipolar disorder and schizophrenia have found overlapping evidence for susceptibility genes in four chromosomal regions-10p12-14, 13q32, 18p11.2, and 22q12-13. The authors previously demonstrated familial clustering of psychotic symptoms-defined as hallucinations and/or delusions-in some bipolar disorder pedigrees. In this study they used stratified linkage analysis to test the hypothesis that those bipolar disorder pedigrees most enriched for psychotic symptoms would show greater evidence of linkage to the regions of previous bipolar disorder/schizophrenia linkage overlap. METHOD: Nonparametric linkage analyses using GENEHUNTER and ASPEX were performed on 65 bipolar disorder families. Family subsets were defined by the number of family members with psychotic mood disorder. RESULTS: The 10 families in which three or more members had psychotic mood disorder showed suggestive evidence of linkage to 13q31 (nonparametric linkage score=3.56; LOD score=2.52) and 22q12 (nonparametric linkage score=3.32; LOD score=3.06). These results differed significantly from those for the entire study group of 65 families, which showed little or no linkage evidence in the two regions. The 10 families with three or more psychotic members did not show evidence of linkage to 10p12-14 or 18p11.2. The 95% confidence interval on 22q12 spanned 4.3 centimorgans (2.6 megabases) and was congruent with previous findings. CONCLUSIONS: Bipolar disorder families in which psychotic symptoms cluster may carry susceptibility genes on chromosomal regions 13q31 and 22q12. Replication should be attempted in similar families and perhaps in schizophrenia families in which mood symptoms cluster because these overlapping phenotypes may correlate most closely with the putative susceptibility genes. The localization of the 22q12 finding particularly encourages further study of this region.
OBJECTIVE: Linkage studies of bipolar disorder and schizophrenia have found overlapping evidence for susceptibility genes in four chromosomal regions-10p12-14, 13q32, 18p11.2, and 22q12-13. The authors previously demonstrated familial clustering of psychotic symptoms-defined as hallucinations and/or delusions-in some bipolar disorder pedigrees. In this study they used stratified linkage analysis to test the hypothesis that those bipolar disorder pedigrees most enriched for psychotic symptoms would show greater evidence of linkage to the regions of previous bipolar disorder/schizophrenia linkage overlap. METHOD: Nonparametric linkage analyses using GENEHUNTER and ASPEX were performed on 65 bipolar disorder families. Family subsets were defined by the number of family members with psychotic mood disorder. RESULTS: The 10 families in which three or more members had psychotic mood disorder showed suggestive evidence of linkage to 13q31 (nonparametric linkage score=3.56; LOD score=2.52) and 22q12 (nonparametric linkage score=3.32; LOD score=3.06). These results differed significantly from those for the entire study group of 65 families, which showed little or no linkage evidence in the two regions. The 10 families with three or more psychotic members did not show evidence of linkage to 10p12-14 or 18p11.2. The 95% confidence interval on 22q12 spanned 4.3 centimorgans (2.6 megabases) and was congruent with previous findings. CONCLUSIONS:Bipolar disorder families in which psychotic symptoms cluster may carry susceptibility genes on chromosomal regions 13q31 and 22q12. Replication should be attempted in similar families and perhaps in schizophrenia families in which mood symptoms cluster because these overlapping phenotypes may correlate most closely with the putative susceptibility genes. The localization of the 22q12 finding particularly encourages further study of this region.
Authors: Hamid Mostafavi Abdolmaleky; Kuang-Hung Cheng; Stephen V Faraone; Marsha Wilcox; Stephen J Glatt; Fangming Gao; Cassandra L Smith; Rahim Shafa; Batol Aeali; Julie Carnevale; Hongjie Pan; Panagiotis Papageorgis; Jose F Ponte; Vadivelu Sivaraman; Ming T Tsuang; Sam Thiagalingam Journal: Hum Mol Genet Date: 2006-09-19 Impact factor: 6.150
Authors: Stephanie Nissen; Sherri Liang; Tatyana Shehktman; John R Kelsoe; Tiffany A Greenwood; Caroline M Nievergelt; Rebecca McKinney; Paul D Shilling; Erin N Smith; Nicholas J Schork; Cinnamon S Bloss; John I Nurnberger; Howard J Edenberg; Tatiana Foroud; Daniel L Koller; Elliot S Gershon; Chunyu Liu; Judith A Badner; William A Scheftner; William B Lawson; Evaristus A Nwulia; Maria Hipolito; William Coryell; John Rice; William Byerley; Francis J McMahon; Wade H Berrettini; James B Potash; Peter P Zandi; Pamela B Mahon; Melvin G McInnis; Sebastian Zöllner; Peng Zhang; David W Craig; Szabolics Szelinger; Thomas B Barrett; Thomas G Schulze Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2012-10-04 Impact factor: 3.568
Authors: M L Hamshere; E K Green; I R Jones; L Jones; V Moskvina; G Kirov; D Grozeva; I Nikolov; D Vukcevic; S Caesar; K Gordon-Smith; C Fraser; E Russell; G Breen; D St Clair; D A Collier; A H Young; I N Ferrier; A Farmer; P McGuffin; P A Holmans; M J Owen; M C O'Donovan; N Craddock Journal: Br J Psychiatry Date: 2009-07 Impact factor: 9.319
Authors: Paul J Fitzgerald; Chris Barkus; Michael Feyder; Lisa M Wiedholz; Yi-Chyan Chen; Rose-Marie Karlsson; Rodrigo Machado-Vieira; Carolyn Graybeal; Trevor Sharp; Carlos Zarate; Judith Harvey-White; Jing Du; Rolf Sprengel; Peter Gass; David Bannerman; Andrew Holmes Journal: Neurobiol Dis Date: 2010-08-08 Impact factor: 5.996