Dataset Information

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

ABSTRACT: 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.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.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.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.

SUBMITTER: Deka R

PROVIDER: S-EPMC2876230 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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

Deka Ranjan R Koller Daniel L DL Lai Dongbing D Indugula Subba Rao SR Sun Guangyun G Woo Daniel D Sauerbeck Laura L Moomaw Charles J CJ Hornung Richard R Connolly E Sander ES Anderson Craig C Rouleau Guy G Meissner Irene I Bailey-Wilson Joan E JE Huston John J Brown Robert D RD Kleindorfer Dawn O DO Flaherty Matthew L ML Langefeld Carl D CD Foroud Tatiana T Broderick Joseph P JP

Stroke 20100226 6

<h4>Background and purpose</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 20190001

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Project description:BackgroundTelomere length is closely linked to the aging phenotype, where cellular aging results in the production of a cascade of cell factors and the senescence-associated secretory phenotype (SASP), leading to an inflammatory response. The presence of inflammation plays a crucial role in the formation of intracranial aneurysms. Nevertheless, the relationship between telomere length and intracranial aneurysms remains unclear. This study aims to explore the causal connection between telomere length and intracranial aneurysms through the utilization of Mendelian randomization (MR) analysis.MethodsData on telomere length were obtained from the genome-wide association studies conducted on the UK Biobank, comprising a total of 472,174 participants. Data on intracranial aneurysms were obtained from the summary dataset of the Global Genome-wide Association Study (GWAS) conducted by the International Stroke Genetics Consortium. The dataset consisted of 7,495 cases and 71,934 controls, all of European descent. Initially, the linkage disequilibrium score was used to investigate the connection between telomere length and intracranial aneurysms. Subsequently, a bidirectional MR was conducted using two-sample analysis to assess whether there is a causal connection between telomere length and intracranial aneurysm risk. The results were analyzed utilizing five MR methods, with the inverse variance weighted method serving as the main methodology. In addition, we did various analyses to evaluate the presence of heterogeneity, pleiotropy, and sensitivity in the study results. A reverse MR analysis was conducted to investigate potential reverse causal links.ResultsIn the forward MR analysis, it was observed that both the inverse variance-weighted and weighted median analyses implied a potential causal relationship between longer telomere length and a decreased incidence of intracranial aneurysms (IVW: OR = 0.66, 95% CI: 0.47-0.92, p = 1.49 × 10-2). There was no heterogeneity or horizontal pleiotropy. The findings were verified to be robust through the utilization of leave-one-out analysis. The use of reverse MR analysis did not establish a potential causal link between the occurrence of intracranial aneurysms and telomere length.ConclusionThere may exist a potential correlation between longer telomere length and a decreased likelihood of intracranial aneurysms within the European population. The present study offers novel insights into the correlation between telomere length and intracranial aneurysms. Additional research is required to clarify the underlying mechanisms and validate our discoveries in diverse populations.

Dataset Information

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

Publications

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

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