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Multicenter Study
. 2010 Jun;41(6):1132-7.
doi: 10.1161/STROKEAHA.109.574640. Epub 2010 Feb 26.

The relationship between smoking and replicated sequence variants on chromosomes 8 and 9 with familial intracranial aneurysm

Ranjan Deka  1 , 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 3rd, Robert D Brown, Dawn O Kleindorfer, Matthew L Flaherty, Carl D Langefeld, Tatiana Foroud, Joseph P Broderick; FIA Study Investigators
Affiliations
Multicenter Study

The relationship between smoking and replicated sequence variants on chromosomes 8 and 9 with familial intracranial aneurysm

Ranjan Deka et al. Stroke. 2010 Jun.

Abstract

Background and purpose: The purpose of this study was to replicate the previous association of single nucleotide polymorphisms (SNPs) with risk of intracranial aneurysm (IA) and to examine the relationship of smoking with these variants and the risk of IA.

Methods: White probands with an IA from families with multiple affected members were identified by 26 clinical centers located throughout North America, New Zealand, and Australia. White control subjects free of stroke and IA were selected by random digit dialing from the Greater Cincinnati population. SNPs previously associated with IA on chromosomes 2, 8, and 9 were genotyped using a TaqMan assay or were included in the Affymetrix 6.0 array that was part of a genomewide association study of 406 IA cases and 392 control subjects. Logistic regression modeling tested whether the association of replicated SNPs with IA was modulated by smoking.

Results: The strongest evidence of association with IA was found with the 8q SNP rs10958409 (genotypic P=9.2x10(-5); allelic P=1.3x10(-5); OR=1.86, 95% CI: 1.40 to 2.47). We also replicated the association with both SNPs on chromosome 9p, rs1333040 and rs10757278, but were not able to replicate the previously reported association of the 2 SNPs on chromosome 2q. Statistical testing showed a multiplicative relationship between the risk alleles and smoking with regard to the risk of IA.

Conclusions: Our data provide complementary evidence that the variants on chromosomes 8q and 9p are associated with IA and that the risk of IA in patients with these variants is greatly increased with cigarette smoking.

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Figures

Figure 1
Figure 1
Plot of all cases who were smokers at any time by pack-years of smoking and age of diagnosis.
Figure 2
Figure 2
All GWAS SNPs 250 kb upstream and downstream of the replicated SNPs are shown in each panel, chromosome 8 in panel A, chromosome 9 in panel B. The dashed horizontal line in each panel indicates the □=0.05 significance threshold correcting for the SNPs in each region by the simpleM method
See this image and copyright information in PMC

References

    1. Bilguvar K, Yasuno K, Niemela M, Ruigrok YM, von Und Zu Fraunberg M, van Duijn CM, van den Berg LH, Mane S, Mason CE, Choi M, Gaal E, Bayri Y, Kolb L, Arlier Z, Ravuri S, Ronkainen A, Tajima A, Laakso A, Hata A, Kasuya H, Koivisto T, Rinne J, Ohman J, Breteler MM, Wijmenga C, State MW, Rinkel GJ, Hernesniemi J, Jaaskelainen JE, Palotie A, Inoue I, Lifton RP, Gunel M. Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nat Genet. 2008;40:1472–1477. - PMC - PubMed
    1. Helgadottir A, Thorleifsson G, Magnusson KP, Gretarsdottir S, Steinthorsdottir V, Manolescu A, Jones GT, Rinkel GJ, Blankensteijn JD, Ronkainen A, Jaaskelainen JE, Kyo Y, Lenk GM, Sakalihasan N, Kostulas K, Gottsater A, Flex A, Stefansson H, Hansen T, Andersen G, Weinsheimer S, Borch-Johnsen K, Jorgensen T, Shah SH, Quyyumi AA, Granger CB, Reilly MP, Austin H, Levey AI, Vaccarino V, Palsdottir E, Walters GB, Jonsdottir T, Snorradottir S, Magnusdottir D, Gudmundsson G, Ferrell RE, Sveinbjornsdottir S, Hernesniemi J, Niemela M, Limet R, Andersen K, Sigurdsson G, Benediktsson R, Verhoeven EL, Teijink JA, Grobbee DE, Rader DJ, Collier DA, Pedersen O, Pola R, Hillert J, Lindblad B, Valdimarsson EM, Magnadottir HB, Wijmenga C, Tromp G, Baas AF, Ruigrok YM, van Rij AM, Kuivaniemi H, Powell JT, Matthiasson SE, Gulcher JR, Thorgeirsson G, Kong A, Thorsteinsdottir U, Stefansson K. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet. 2008;40:217–224. - PubMed
    1. Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, Jonasdottir A, Sigurdsson A, Baker A, Palsson A, Masson G, Gudbjartsson DF, Magnusson KP, Andersen K, Levey AI, Backman VM, Matthiasdottir S, Jonsdottir T, Palsson S, Einarsdottir H, Gunnarsdottir S, Gylfason A, Vaccarino V, Hooper WC, Reilly MP, Granger CB, Austin H, Rader DJ, Shah SH, Quyyumi AA, Gulcher JR, Thorgeirsson G, Thorsteinsdottir U, Kong A, Stefansson K. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007;316:1491–1493. - PubMed
    1. Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE, Barrett JH, Konig IR, Stevens SE, Szymczak S, Tregouet DA, Iles MM, Pahlke F, Pollard H, Lieb W, Cambien F, Fischer M, Ouwehand W, Blankenberg S, Balmforth AJ, Baessler A, Ball SG, Strom TM, Braenne I, Gieger C, Deloukas P, Tobin MD, Ziegler A, Thompson JR, Schunkert H, WTCCC and the Cardiogenics Consortium Genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357:443–453. - PMC - PubMed
    1. McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC. A common allele on chromosome 9 associated with coronary heart disease. Science. 2007;316:1488–1491. - PMC - PubMed

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