ArticlePLoS genetics2014
High risk population isolate reveals low frequency variants predisposing to intracranial aneurysms.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Genome-Wide Meta-Analysis of Sciatica in Finnish Population.PloS one · 2016Pooled it
- Whole-exome analysis in Tunisian Imazighen and Arabs shows the impact of demography in functional variation.Scientific reports · 2021Trial
- Epigenetic mechanisms in aneurysm formation, growth, and rupture: A systematic review.Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences · 2025Review
- Heritability of complex traits in sub-populations experiencing bottlenecks and growth.Journal of human genetics · 2024Article
- Long-term Risk of Epilepsy in Subarachnoid Hemorrhage Survivors With Positive Family History: A Population-Based Follow-up Study.Neurology · 2023Article
- Inefficient splicing of long non-coding RNAs is associated with higher transcript complexity in human and mouse.RNA biology · 2023Article
- Genome-wide linkage analysis combined with genome sequencing in large families with intracranial aneurysms.European journal of human genetics : EJHG · 2022Article
- Endogenous animal models of intracranial aneurysm development: a review.Neurosurgical review · 2021Review
- Epigenetic landscapes of intracranial aneurysm risk haplotypes implicate enhancer function of endothelial cells and fibroblasts in dysregulated gene expression.BMC medical genomics · 2021Article
- Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.Nature genetics · 2020Article
- Exome-chip association analysis of intracranial aneurysms.Neurology · 2020Article
- Intracranial Aneurysms: Pathology, Genetics, and Molecular Mechanisms.Neuromolecular medicine · 2019Review
- Epigenetic landscapes suggest that genetic risk for intracranial aneurysm operates on the endothelium.BMC medical genomics · 2019Article
- Associations among Genetic Variants and Intracranial Aneurysm in a Chinese Population.Yonsei medical journal · 2019Article
- Genome-Wide Association between the 2q33.1 Locus and Intracranial Aneurysm Susceptibility: An Updated Meta-Analysis Including 18,019 Individuals.Journal of clinical medicine · 2019Article
- Rho Guanine Nucleotide Exchange FactorCirculation. Genomic and precision medicine · 2018Article
- Rare and Low-Frequency Variant ofCirculation. Genomic and precision medicine · 2018Article
- Genome-wide association analysis identifies new candidate risk loci for familial intracranial aneurysm in the French-Canadian population.Scientific reports · 2018Article
- Identification of six polymorphisms as novel susceptibility loci for ischemic or hemorrhagic stroke by exome-wide association studies.International journal of molecular medicine · 2017Article
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Authors and funding
35 authors at 14 institutions in 6 countries.
Funding
Abstract
3% of the population develops saccular intracranial aneurysms (sIAs), a complex trait, with a sporadic and a familial form. Subarachnoid hemorrhage from sIA (sIA-SAH) is a devastating form of stroke. Certain rare genetic variants are enriched in the Finns, a population isolate with a small founder population and bottleneck events. As the sIA-SAH incidence in Finland is >2× increased, such variants may associate with sIA in the Finnish population. We tested 9.4 million variants for association in 760 Finnish sIA patients (enriched for familial sIA), and in 2,513 matched controls with case-control status and with the number of sIAs. The most promising loci (p<5E-6) were replicated in 858 Finnish sIA patients and 4,048 controls. The frequencies and effect sizes of the replicated variants were compared to a continental European population using 717 Dutch cases and 3,004 controls. We discovered four new high-risk loci with low frequency lead variants. Three were associated with the case-control status: 2q23.3 (MAF 2.1%, OR 1.89, p 1.42×10-9); 5q31.3 (MAF 2.7%, OR 1.66, p 3.17×10-8); 6q24.2 (MAF 2.6%, OR 1.87, p 1.87×10-11) and one with the number of sIAs: 7p22.1 (MAF 3.3%, RR 1.59, p 6.08×-9). Two of the associations (5q31.3, 6q24.2) replicated in the Dutch sample. The 7p22.1 locus was strongly differentiated; the lead variant was more frequent in Finland (4.6%) than in the Netherlands (0.3%). Additionally, we replicated a previously inconclusive locus on 2q33.1 in all samples tested (OR 1.27, p 1.87×10-12). The five loci explain 2.1% of the sIA heritability in Finland, and may relate to, but not explain, the increased incidence of sIA-SAH in Finland. This study illustrates the utility of population isolates, familial enrichment, dense genotype imputation and alternate phenotyping in search for variants associated with complex diseases.
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