BACKGROUND AND PURPOSE: Evidence supports a substantial genetic contribution to the risk of intracranial aneurysm (IA). The purpose of this study was to identify chromosomal regions likely to harbor genes that contribute to the risk of IA. METHODS: Multiplex families having at least 2 individuals with "definite" or "probable" IA were ascertained through an international consortium. First-degree relatives of individuals with IA who were at increased risk of an IA because of a history of hypertension or present smoking were offered cerebral magnetic resonance angiography. A genome screen was completed using the Illumina 6K SNP system, and the resulting data from 192 families, containing 1155 genotyped individuals, were analyzed. Narrow and broad disease definitions were used when testing for linkage using multipoint model-independent methods. Ordered subset analysis was performed to test for a gene x smoking (pack-years) interaction. RESULTS: The greatest evidence of linkage was found on chromosomes 4 (LOD=2.5; 156 cM), 7 (LOD=1.7; 183 cM), 8 (LOD=1.9; 70 cM), and 12 (LOD=1.6; 102 cM) using the broad disease definition. Using the average pack-years for the affected individuals in each family, the genes on chromosomes 4 (LOD=3.5; P=0.03), 7 (LOD=4.1; P=0.01) and 12 (LOD=3.6; P=0.02) all appear to be modulated by the degree of smoking in the affected members of the family. On chromosome 8, inclusion of smoking as a covariate did not significantly strengthen the linkage evidence, suggesting no interaction between the loci in this region and smoking. CONCLUSIONS: We have detected possible evidence of linkage to 4 chromosomal regions. There is potential evidence for a gene x smoking interaction with 3 of the loci.
BACKGROUND AND PURPOSE: Evidence supports a substantial genetic contribution to the risk of intracranial aneurysm (IA). The purpose of this study was to identify chromosomal regions likely to harbor genes that contribute to the risk of IA. METHODS: Multiplex families having at least 2 individuals with "definite" or "probable" IA were ascertained through an international consortium. First-degree relatives of individuals with IA who were at increased risk of an IA because of a history of hypertension or present smoking were offered cerebral magnetic resonance angiography. A genome screen was completed using the Illumina 6K SNP system, and the resulting data from 192 families, containing 1155 genotyped individuals, were analyzed. Narrow and broad disease definitions were used when testing for linkage using multipoint model-independent methods. Ordered subset analysis was performed to test for a gene x smoking (pack-years) interaction. RESULTS: The greatest evidence of linkage was found on chromosomes 4 (LOD=2.5; 156 cM), 7 (LOD=1.7; 183 cM), 8 (LOD=1.9; 70 cM), and 12 (LOD=1.6; 102 cM) using the broad disease definition. Using the average pack-years for the affected individuals in each family, the genes on chromosomes 4 (LOD=3.5; P=0.03), 7 (LOD=4.1; P=0.01) and 12 (LOD=3.6; P=0.02) all appear to be modulated by the degree of smoking in the affected members of the family. On chromosome 8, inclusion of smoking as a covariate did not significantly strengthen the linkage evidence, suggesting no interaction between the loci in this region and smoking. CONCLUSIONS: We have detected possible evidence of linkage to 4 chromosomal regions. There is potential evidence for a gene x smoking interaction with 3 of the loci.
Authors: Elizabeth R Hauser; Richard M Watanabe; William L Duren; Meredyth P Bass; Carl D Langefeld; Michael Boehnke Journal: Genet Epidemiol Date: 2004-07 Impact factor: 2.135
Authors: Nicole Berthelemy-Okazaki; Yu Zhao; Zhenglin Yang; Nicola J Camp; Jim Farnham; Dennis Parker; Jay Tsuruda; Joel Macdonald; Kang Zhang; Lisa A Cannon-Albright Journal: Stroke Date: 2005-05-12 Impact factor: 7.914
Authors: Anne Hofer; Marcella Hermans; Nina Kubassek; Matthias Sitzer; Harald Funke; Florian Stögbauer; Vytautas Ivaskevicius; Johannes Oldenburg; Johannes Burtscher; Ulrich Knopp; Beate Schoch; Isabel Wanke; Felix Hübner; Wolfgang Deinsberger; Bernhard Meyer; Hans Boecher-Schwarz; Werner Poewe; Andreas Raabe; Helmuth Steinmetz; Georg Auburger Journal: Stroke Date: 2003-04-10 Impact factor: 7.914
Authors: James M Farnham; Nicola J Camp; Susan L Neuhausen; Jay Tsuruda; Dennis Parker; Joel MacDonald; Lisa A Cannon-Albright Journal: Hum Genet Date: 2003-11-06 Impact factor: 4.132
Authors: Kimon Bekelis; Joanna S Kerley-Hamilton; Amy Teegarden; Craig R Tomlinson; Rachael Kuintzle; Nathan Simmons; Robert J Singer; David W Roberts; Manolis Kellis; David A Hendrix Journal: J Neurosurg Date: 2016-02-26 Impact factor: 5.115
Authors: Ellen Regalado; Sarah Medrek; Van Tran-Fadulu; Dong-Chuan Guo; Hariyadarshi Pannu; Hossein Golabbakhsh; Suzanne Smart; Julia H Chen; Sanjay Shete; Dong H Kim; Ralph Stern; Alan C Braverman; Dianna M Milewicz Journal: Am J Med Genet A Date: 2011-08-03 Impact factor: 2.802
Authors: Oswaldo Lorenzo-Betancor; Patrick R Blackburn; Emily Edwards; Rocío Vázquez-do-Campo; Eric W Klee; Catherine Labbé; Kyndall Hodges; Patrick Glover; Ashley N Sigafoos; Alexandra I Soto; Ronald L Walton; Stephen Doxsey; Michael B Bober; Sarah Jennings; Karl J Clark; Yan Asmann; David Miller; William D Freeman; James Meschia; Owen A Ross Journal: Neurology Date: 2018-11-09 Impact factor: 9.910
Authors: Ranjan Deka; Daniel L Koller; Dongbing Lai; Subba Rao Indugula; Guangyun Sun; Daniel Woo; Laura Sauerbeck; Charles J Moomaw; Richard Hornung; E Sander Connolly; Craig Anderson; Guy Rouleau; Irene Meissner; Joan E Bailey-Wilson; John Huston; Robert D Brown; Dawn O Kleindorfer; Matthew L Flaherty; Carl D Langefeld; Tatiana Foroud; Joseph P Broderick Journal: Stroke Date: 2010-02-26 Impact factor: 7.914
Authors: Kaya Bilguvar; Katsuhito Yasuno; Mika Niemelä; Ynte M Ruigrok; Mikael von Und Zu Fraunberg; Cornelia M van Duijn; Leonard H van den Berg; Shrikant Mane; Christopher E Mason; Murim Choi; Emília Gaál; Yasar Bayri; Luis Kolb; Zulfikar Arlier; Sudhakar Ravuri; Antti Ronkainen; Atsushi Tajima; Aki Laakso; Akira Hata; Hidetoshi Kasuya; Timo Koivisto; Jaakko Rinne; Juha Ohman; Monique M B Breteler; Cisca Wijmenga; Matthew W State; Gabriel J E Rinkel; Juha Hernesniemi; Juha E Jääskeläinen; Aarno Palotie; Ituro Inoue; Richard P Lifton; Murat Günel Journal: Nat Genet Date: 2008-11-09 Impact factor: 38.330
Authors: Daniel L Cooke; David B McCoy; Van V Halbach; Steven W Hetts; Matthew R Amans; Christopher F Dowd; Randall T Higashida; Devon Lawson; Jeffrey Nelson; Chih-Yang Wang; Helen Kim; Zena Werb; Charles McCulloch; Tomoki Hashimoto; Hua Su; Zhengda Sun Journal: Transl Stroke Res Date: 2017-09-13 Impact factor: 6.829
Authors: Tatiana Foroud; Daniel L Koller; Dongbing Lai; Laura Sauerbeck; Craig Anderson; Nerissa Ko; Ranjan Deka; Thomas H Mosley; Myriam Fornage; Daniel Woo; Charles J Moomaw; Richard Hornung; John Huston; Irene Meissner; Joan E Bailey-Wilson; Carl Langefeld; Guy Rouleau; E Sander Connolly; Bradford B Worrall; Dawn Kleindorfer; Matthew L Flaherty; Sharyl Martini; Jason Mackey; Felipe De Los Rios La Rosa; Robert D Brown; Joseph P Broderick Journal: Stroke Date: 2012-09-06 Impact factor: 7.914
Authors: Laura Sauerbeck; Richard Hornung; Daniel Woo; Charles J Moomaw; Craig Anderson; E Sander Connolly; Guy A Rouleau; Robert D Brown; Joseph P Broderick Journal: Int J Stroke Date: 2012-08-29 Impact factor: 5.266
Authors: Bradford B Worrall; Tatiana Foroud; Robert D Brown; E Sander Connolly; Richard W Hornung; John Huston; Dawn Kleindorfer; Daniel L Koller; Dongbing Lai; Charles J Moomaw; Laura Sauerbeck; Daniel Woo; Joseph P Broderick Journal: Stroke Date: 2008-10-23 Impact factor: 7.914