TY - JOUR
T1 - Genome screen in familial intracranial aneurysm
AU - FIA Study Investigators
AU - Foroud, Tatiana
AU - Sauerbeck, Laura
AU - Brown, Robert
AU - Anderson, Craig
AU - Woo, Daniel
AU - Kleindorfer, Dawn
AU - Flaherty, Matthew L.
AU - Deka, Ranjan
AU - Hornung, Richard
AU - Meissner, Irene
AU - Bailey-Wilson, Joan E.
AU - Langefeld, Carl
AU - Rouleau, Guy
AU - Connolly, E. Sander
AU - Lai, Dongbing
AU - Koller, Daniel L.
AU - Huston, John
AU - Broderick, Joseph P.
AU - Fisher, W.
AU - Forson, H.
AU - Mee, E.
AU - Howe, C.
AU - Vos, S.
AU - Hankey, G.
AU - Knuckey, N.
AU - Laidlaw, J.
AU - Reilly, P.
AU - Dorsch, N.
AU - Morgan, M.
AU - Besser, M.
AU - Rosenfeld, J.
AU - Athanasiadis, K.
AU - Claxton, A.
AU - Dunne, V.
AU - Griffith, J.
AU - Davidson, J.
AU - Pope, S.
AU - Froelich, Amanda
AU - Day, A.
AU - Brach, R.
AU - Zuccarello, M.
AU - Ringer, A.
AU - Yeh, H.
AU - Franklin, K.
AU - Ramussen, P.
AU - Andrews-Hinders, D.
AU - Wheeler, T.
AU - Sacco, R.
AU - Lamonica, D.
AU - Lewis, S. B.
AU - Royster, A.
AU - Payner, T.
AU - Miracle, N.
AU - Murphy, K.
AU - Kohler, B.
AU - Ogilvy, C.
AU - Buckley, D.
AU - Manansala, J.
AU - Ferguson, G.
AU - Mayer, C.
AU - Peacock, J.
AU - Desjarlais, A.
AU - Aldrich, E. F.
AU - Aldrich, C.
AU - Byard, C.
AU - Brown, R. D.
AU - Jaeger, L.
AU - Morgenstern, L.
AU - Concannon, M.
AU - Qureshi, A. I.
AU - Harris-Lane, P.
AU - Batjer, H.
AU - Joven, G.
AU - Thompson, S.
AU - Richard, M. T.
AU - Hopper, A.
AU - Kassam, A. B.
AU - Lee, K.
AU - Johnston, C.
AU - Katsura, K.
AU - Giannotta, S.
AU - Fishback, D.
AU - Steinberg, G.
AU - Luu, D.
AU - Coburn, M.
AU - Malkoff, M.
AU - Wojner, A.
AU - Kassel, N.
AU - Worrall, B.
AU - Radakovic, G.
AU - Tirschwell, D.
AU - Tanzi, P.
AU - Derdeyn, C.
AU - Catanzaro, M.
AU - Kaufmann, A.
AU - Gladish, D.
N1 - Publisher Copyright:
© 2009 Foroud et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
PY - 2009/1/1
Y1 - 2009/1/1
N2 - Background: Individuals with 1st degree relatives harboring an intracranial aneurysm (IA) are at an increased risk of IA, suggesting genetic variation is an important risk factor. Methods: Families with multiple members having ruptured or unruptured IA were recruited and all available medical records and imaging data were reviewed to classify possible IA subjects as definite, probable or possible IA or not a case. A 6 K SNP genome screen was performed in 333 families, representing the largest linkage study of IA reported to date. A 'narrow' (n = 705 definite IA cases) and 'broad' (n = 866 definite or probable IA) disease definition were used in multipoint model-free linkage analysis and parametric linkage analysis, maximizing disease parameters. Ordered subset analysis (OSA) was used to detect gene × smoking interaction. Results: Model-free linkage analyses detected modest evidence of possible linkage (all LOD < 1.5). Parametric analyses yielded an unadjusted LOD score of 2.6 on chromosome 4q (162 cM) and 3.1 on chromosome 12p (50 cM). Significant evidence for a gene × smoking interaction was detected using both disease models on chromosome 7p (60 cM; p ≤ 0.01). Our study provides modest evidence of possible linkage to several chromosomes. Conclusion: These data suggest it is unlikely that there is a single common variant with a strong effect in the majority of the IA families. Rather, it is likely that multiple genetic and environmental risk factors contribute to the susceptibility for intracranial aneurysms.
AB - Background: Individuals with 1st degree relatives harboring an intracranial aneurysm (IA) are at an increased risk of IA, suggesting genetic variation is an important risk factor. Methods: Families with multiple members having ruptured or unruptured IA were recruited and all available medical records and imaging data were reviewed to classify possible IA subjects as definite, probable or possible IA or not a case. A 6 K SNP genome screen was performed in 333 families, representing the largest linkage study of IA reported to date. A 'narrow' (n = 705 definite IA cases) and 'broad' (n = 866 definite or probable IA) disease definition were used in multipoint model-free linkage analysis and parametric linkage analysis, maximizing disease parameters. Ordered subset analysis (OSA) was used to detect gene × smoking interaction. Results: Model-free linkage analyses detected modest evidence of possible linkage (all LOD < 1.5). Parametric analyses yielded an unadjusted LOD score of 2.6 on chromosome 4q (162 cM) and 3.1 on chromosome 12p (50 cM). Significant evidence for a gene × smoking interaction was detected using both disease models on chromosome 7p (60 cM; p ≤ 0.01). Our study provides modest evidence of possible linkage to several chromosomes. Conclusion: These data suggest it is unlikely that there is a single common variant with a strong effect in the majority of the IA families. Rather, it is likely that multiple genetic and environmental risk factors contribute to the susceptibility for intracranial aneurysms.
UR - http://www.scopus.com/inward/record.url?scp=59649123940&partnerID=8YFLogxK
U2 - 10.1186/1471-2350-10-3
DO - 10.1186/1471-2350-10-3
M3 - Article
C2 - 19144135
AN - SCOPUS:59649123940
SN - 1471-2350
VL - 10
JO - BMC Medical Genetics
JF - BMC Medical Genetics
IS - 3
M1 - 3
ER -