Genome-wide association study reveals three susceptibility loci for common migraine in the general population
Markus Schürks and colleagues report a genome-wide association study for common migraine. They identify three new susceptibility loci at PRDM16 , TRPM8 and LRP1 . Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic...
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| Vydané v: | Nature genetics Ročník 43; číslo 7; s. 695 - 698 |
|---|---|
| Hlavní autori: | , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
New York
Nature Publishing Group US
01.07.2011
Nature Publishing Group |
| Predmet: | |
| ISSN: | 1061-4036, 1546-1718, 1546-1718 |
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| Abstract | Markus Schürks and colleagues report a genome-wide association study for common migraine. They identify three new susceptibility loci at
PRDM16
,
TRPM8
and
LRP1
.
Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32,
PRDM16
), rs10166942 (2q37.1,
TRPM8
) and rs11172113 (12q13.3,
LRP1
) were among the top seven associations (
P
< 5 × 10
−6
) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11,
P
= 3.8 × 10
−9
; rs10166942, OR = 0.85,
P
= 5.5 × 10
−12
; and rs11172113, OR = 0.90,
P
= 4.3 × 10
−9
). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features.
TRPM8
has been the focus of neuropathic pain models, whereas
LRP1
modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology. |
|---|---|
| AbstractList | Markus Schürks and colleagues report a genome-wide association study for common migraine. They identify three new susceptibility loci at
PRDM16
,
TRPM8
and
LRP1
.
Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32,
PRDM16
), rs10166942 (2q37.1,
TRPM8
) and rs11172113 (12q13.3,
LRP1
) were among the top seven associations (
P
< 5 × 10
−6
) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11,
P
= 3.8 × 10
−9
; rs10166942, OR = 0.85,
P
= 5.5 × 10
−12
; and rs11172113, OR = 0.90,
P
= 4.3 × 10
−9
). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features.
TRPM8
has been the focus of neuropathic pain models, whereas
LRP1
modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology. In a population-based genome-wide analysis including 5122 migraineurs and 18,108 non-migraineurs, rs2651899 (PRDM16), rs10166942 (TRMP8), and rs11172113 (LRP1) were among the top associations (p<5×10−6) with migraine. All three SNPs were significant in meta-analysis among replication cohorts and met genome-wide significance (p<4.3×10−9) in meta-analysis combining discovery and replication cohorts. Rs2651899 and rs10166942 associated with migraine compared to non-migraine headache; none of the three SNPs specifically associated with migraine subtypes or features. Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 × 10(-6)) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 × 10(-9); rs10166942, OR = 0.85, P = 5.5 × 10(-12); and rs11172113, OR = 0.90, P = 4.3 × 10(-9)). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology.Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 × 10(-6)) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 × 10(-9); rs10166942, OR = 0.85, P = 5.5 × 10(-12); and rs11172113, OR = 0.90, P = 4.3 × 10(-9)). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology. Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 10 super(-6)) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 10 super(-9); rs10166942, OR = 0.85, P = 5.5 10 super(-12); and rs11172113, OR = 0.90, P = 4.3 10 super(-9)). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology. Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 x [10.sup.-6)] with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 x [10.sup.-9]; rs10166942, OR = 0.85, P = 5.5 x [10.sup.-12]; and rs11172113, OR = 0.90, P = 4.3 x [10.sup.-9]). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology. Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 × 10^sup -6^) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 × 10^sup -9^; rs10166942, OR = 0.85, P = 5.5 × 10^sup -12^; and rs11172113, OR = 0.90, P = 4.3 × 10^sup -9^). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology. [PUBLICATION ABSTRACT] Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 × 10(-6)) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 × 10(-9); rs10166942, OR = 0.85, P = 5.5 × 10(-12); and rs11172113, OR = 0.90, P = 4.3 × 10(-9)). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology. |
| Audience | Academic |
| Author | Schürks, Markus Anttila, Verneri Völzke, Henry Ernst, Florian Kallela, Mikko Ferrari, Michel D Launer, Lenore J Palotie, Aarno Griffiths, Lyn R Freilinger, Tobias van den Maagdenberg, Arn M J M Kubisch, Christian Ridker, Paul M de Vries, Boukje Schminke, Ulf Fendrich, Konstanze Terwindt, Gisela M Hoffmann, Wolfgang Buring, Julie E Chasman, Daniel I Zee, Robert Y L Kurth, Tobias |
| AuthorAffiliation | 3 Department of Neurology, University Hospital Essen, Germany 19 The Broad Institute of MIT and Harvard, Boston, Massachusetts, USA 1 Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA 12 Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University, Greifswald, Germany 8 National Institute of Aging, Laboratory for Epidemiology, Demography, and Biometry, Bethesda, Maryland, USA 9 Department of Neurology, Leiden University Medical Centre, The Netherlands 7 Department of Neurology, Ernst-Moritz-Arndt-University, Greifswald, Germany 20 INSERM Unit 708 – Neuroepidemiology, Paris, France 2 Donald W. Reynolds Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA 15 Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians-Universität and Institute for Stroke and Dementia Research, Klinikum der Universität München, Munich, Germany 10 Insti |
| AuthorAffiliation_xml | – name: 3 Department of Neurology, University Hospital Essen, Germany – name: 4 Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK – name: 16 Institute of Human Genetics, University of Ulm, Ulm, Germany – name: 5 Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland – name: 10 Institute for Community Medicine, Section Epidemiology of Health Care and Community Health, Ernst-Moritz-Arndt-University, Greifswald, Germany – name: 21 UPMC Univ Paris 06, F-75005, Paris, France – name: 14 Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland – name: 19 The Broad Institute of MIT and Harvard, Boston, Massachusetts, USA – name: 18 Department of Medical Genetics, Helsinki University Central Hospital, Helsinki, Finland – name: 8 National Institute of Aging, Laboratory for Epidemiology, Demography, and Biometry, Bethesda, Maryland, USA – name: 17 Department of Medical Genetics, University of Helsinki, Helsinki, Finland – name: 6 Department of Human Genetics, Leiden University Medical Centre, The Netherlands – name: 9 Department of Neurology, Leiden University Medical Centre, The Netherlands – name: 1 Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA – name: 7 Department of Neurology, Ernst-Moritz-Arndt-University, Greifswald, Germany – name: 11 Institute for Community Medicine, Section Clinical Epidemiological Research, Ernst-Moritz-Arndt-University, Greifswald, Germany – name: 15 Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians-Universität and Institute for Stroke and Dementia Research, Klinikum der Universität München, Munich, Germany – name: 12 Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University, Greifswald, Germany – name: 2 Donald W. Reynolds Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA – name: 13 Genomics Research Centre, Griffith Health Institute, Griffith University, Gold Coast, 4222, Qld, Australia – name: 20 INSERM Unit 708 – Neuroepidemiology, Paris, France |
| Author_xml | – sequence: 1 givenname: Daniel I surname: Chasman fullname: Chasman, Daniel I organization: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Donald W. Reynolds Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School – sequence: 2 givenname: Markus surname: Schürks fullname: Schürks, Markus email: markus.schuerks@post.harvard.edu organization: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Department of Neurology, University Hospital Essen – sequence: 3 givenname: Verneri surname: Anttila fullname: Anttila, Verneri organization: Wellcome Trust Sanger Institute, Institute for Molecular Medicine Finland (FIMM), University of Helsinki – sequence: 4 givenname: Boukje surname: de Vries fullname: de Vries, Boukje organization: Department of Human Genetics, Leiden University Medical Centre – sequence: 5 givenname: Ulf surname: Schminke fullname: Schminke, Ulf organization: Department of Neurology, Ernst-Moritz-Arndt University – sequence: 6 givenname: Lenore J surname: Launer fullname: Launer, Lenore J organization: National Institute of Aging, Laboratory for Epidemiology, Demography, and Biometry – sequence: 7 givenname: Gisela M surname: Terwindt fullname: Terwindt, Gisela M organization: Department of Neurology, Leiden University Medical Centre – sequence: 8 givenname: Arn M J M surname: van den Maagdenberg fullname: van den Maagdenberg, Arn M J M organization: Department of Human Genetics, Leiden University Medical Centre, Department of Neurology, Leiden University Medical Centre – sequence: 9 givenname: Konstanze surname: Fendrich fullname: Fendrich, Konstanze organization: Institute for Community Medicine, Section Epidemiology of Health Care and Community Health, Ernst-Moritz-Arndt University – sequence: 10 givenname: Henry surname: Völzke fullname: Völzke, Henry organization: Institute for Community Medicine, Section Clinical Epidemiological Research, Ernst-Moritz-Arndt University – sequence: 11 givenname: Florian surname: Ernst fullname: Ernst, Florian organization: Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt University – sequence: 12 givenname: Lyn R surname: Griffiths fullname: Griffiths, Lyn R organization: Genomics Research Centre, Griffith Health Institute, Griffith University, Gold Coast – sequence: 13 givenname: Julie E surname: Buring fullname: Buring, Julie E organization: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School – sequence: 14 givenname: Mikko surname: Kallela fullname: Kallela, Mikko organization: Department of Neurology, Helsinki University Central Hospital – sequence: 15 givenname: Tobias surname: Freilinger fullname: Freilinger, Tobias organization: Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians-Universität and Institute for Stroke and Dementia Research, Klinikum der Universität München – sequence: 16 givenname: Christian surname: Kubisch fullname: Kubisch, Christian organization: Institute of Human Genetics, University of Ulm – sequence: 17 givenname: Paul M surname: Ridker fullname: Ridker, Paul M organization: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Donald W. Reynolds Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School – sequence: 18 givenname: Aarno surname: Palotie fullname: Palotie, Aarno organization: Wellcome Trust Sanger Institute, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Department of Medical Genetics, University of Helsinki, Department of Medical Genetics, Helsinki University Central Hospital, The Broad Institute of MIT and Harvard – sequence: 19 givenname: Michel D surname: Ferrari fullname: Ferrari, Michel D organization: Department of Neurology, Leiden University Medical Centre – sequence: 20 givenname: Wolfgang surname: Hoffmann fullname: Hoffmann, Wolfgang organization: Institute for Community Medicine, Section Epidemiology of Health Care and Community Health, Ernst-Moritz-Arndt University – sequence: 21 givenname: Robert Y L surname: Zee fullname: Zee, Robert Y L organization: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School – sequence: 22 givenname: Tobias surname: Kurth fullname: Kurth, Tobias email: tobias.kurth@inserm.fr organization: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, INSERM Unit 708—Neuroepidemiology, UPMC Univ Paris 06 |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24333645$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/21666692$$D View this record in MEDLINE/PubMed |
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| Keywords | Vascular disease Nervous system diseases Pain Migraine Central nervous system disease Cardiovascular disease Locus Cerebrovascular disease Cerebral disorder |
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| Snippet | Markus Schürks and colleagues report a genome-wide association study for common migraine. They identify three new susceptibility loci at
PRDM16
,
TRPM8
and... Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the... In a population-based genome-wide analysis including 5122 migraineurs and 18,108 non-migraineurs, rs2651899 (PRDM16), rs10166942 (TRMP8), and rs11172113 (LRP1)... |
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| Title | Genome-wide association study reveals three susceptibility loci for common migraine in the general population |
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