Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
Copyright policy )Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.
- Centre Hospitalier Régional Universitaire de Brest France
- University of Michigan–Ann Arbor United States
- National Institute for Health Research United Kingdom
- Utrecht University Netherlands
- Technical University of Munich Germany
genetics [Blood Pressure], Medizin, BioBank Japan Project Consortium, Blood Pressure, Cardiovascular, Subarachnoid Hemorrhage/genetics, Medical and Health Sciences, Risk Factors, physiopathology [Hypertension], Smoking/adverse effects, 2.1 Biological and endogenous factors, Aetiology, European Continental Ancestry Group/genetics, genetics [Genetic Predisposition to Disease], CADISP Group, Genetic Predisposition to Disease/genetics, Research Support, Non-U.S. Gov't, Endothelial Cells/pathology, Smoking, Single Nucleotide, genetics [Smoking], Biological Sciences, Polymorphism, Single Nucleotide/genetics, genetics [Intracranial Aneurysm], Stroke, [SDV] Life Sciences [q-bio], genetics [European Continental Ancestry Group], Hypertension, genetics [Polymorphism, Single Nucleotide], 616.8, Blood Pressure/genetics, pathology [Intracranial Aneurysm], genetics [White People], 616.07, pathology [Endothelial Cells], Polymorphism, Single Nucleotide, International Stroke Genetics Consortium, White People, Research Support, N.I.H., Extramural, Asian People, Clinical Research, 616, Genetics, Journal Article, ICAN Study Group, Humans, Asian Continental Ancestry Group/genetics, Genetic Predisposition to Disease, Polymorphism, China Kadoorie Biobank Collaborative Group, Intracranial Aneurysm/genetics, genetics [Subarachnoid Hemorrhage], genetics [Asian Continental Ancestry Group], Prevention, Human Genome, genetics [Asian People], pathology [Subarachnoid Hemorrhage], Neurosciences, adverse effects [Smoking], Neurology - Radboud University Medical Center, Endothelial Cells, Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical Neuroscience, Intracranial Aneurysm, Subarachnoid Hemorrhage, Brain Disorders, Case-Control Studies, HUNT All-In Stroke, genetics [Hypertension], Hypertension/genetics, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study investigators, Developmental Biology, Genome-Wide Association Study, ddc: ddc:616.07, ddc: ddc:570, ddc: ddc:616.8
genetics [Blood Pressure], Medizin, BioBank Japan Project Consortium, Blood Pressure, Cardiovascular, Subarachnoid Hemorrhage/genetics, Medical and Health Sciences, Risk Factors, physiopathology [Hypertension], Smoking/adverse effects, 2.1 Biological and endogenous factors, Aetiology, European Continental Ancestry Group/genetics, genetics [Genetic Predisposition to Disease], CADISP Group, Genetic Predisposition to Disease/genetics, Research Support, Non-U.S. Gov't, Endothelial Cells/pathology, Smoking, Single Nucleotide, genetics [Smoking], Biological Sciences, Polymorphism, Single Nucleotide/genetics, genetics [Intracranial Aneurysm], Stroke, [SDV] Life Sciences [q-bio], genetics [European Continental Ancestry Group], Hypertension, genetics [Polymorphism, Single Nucleotide], 616.8, Blood Pressure/genetics, pathology [Intracranial Aneurysm], genetics [White People], 616.07, pathology [Endothelial Cells], Polymorphism, Single Nucleotide, International Stroke Genetics Consortium, White People, Research Support, N.I.H., Extramural, Asian People, Clinical Research, 616, Genetics, Journal Article, ICAN Study Group, Humans, Asian Continental Ancestry Group/genetics, Genetic Predisposition to Disease, Polymorphism, China Kadoorie Biobank Collaborative Group, Intracranial Aneurysm/genetics, genetics [Subarachnoid Hemorrhage], genetics [Asian Continental Ancestry Group], Prevention, Human Genome, genetics [Asian People], pathology [Subarachnoid Hemorrhage], Neurosciences, adverse effects [Smoking], Neurology - Radboud University Medical Center, Endothelial Cells, Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical Neuroscience, Intracranial Aneurysm, Subarachnoid Hemorrhage, Brain Disorders, Case-Control Studies, HUNT All-In Stroke, genetics [Hypertension], Hypertension/genetics, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study investigators, Developmental Biology, Genome-Wide Association Study, ddc: ddc:616.07, ddc: ddc:570, ddc: ddc:616.8
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