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Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families.
Gormley, Padhraig; Kurki, Mitja I; Hiekkala, Marjo Eveliina; Veerapen, Kumar; Häppölä, Paavo; Mitchell, Adele A; Lal, Dennis; Palta, Priit; Surakka, Ida; Kaunisto, Mari Anneli; Hämäläinen, Eija; Vepsäläinen, Salli; Havanka, Hannele; Harno, Hanna; Ilmavirta, Matti; Nissilä, Markku; Säkö, Erkki; Sumelahti, Marja-Liisa; Liukkonen, Jarmo; Sillanpää, Matti; Metsähonkala, Liisa; Koskinen, Seppo; Lehtimäki, Terho; Raitakari, Olli; Männikkö, Minna; Ran, Caroline; Belin, Andrea Carmine; Jousilahti, Pekka; Anttila, Verneri; Salomaa, Veikko; Artto, Ville; Färkkilä, Markus; Runz, Heiko; Daly, Mark J; Neale, Benjamin M; Ripatti, Samuli; Kallela, Mikko; Wessman, Maija; Palotie, Aarno.
Afiliação
  • Gormley P; Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kurki MI; Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hiekkala ME; Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
  • Veerapen K; Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Häppölä P; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
  • Mitchell AA; Merck Research Laboratories, Merck and Co., Kenilworth, NJ, USA.
  • Lal D; Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Cologne Center for Genomics, University of Cologne, Cologne, Germany.
  • Palta P; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
  • Surakka I; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
  • Kaunisto MA; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
  • Hämäläinen E; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
  • Vepsäläinen S; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
  • Havanka H; Regional State Administrative Agency for Northern Finland, Oulu, Finland.
  • Harno H; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland; Division of Pain Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Finland.
  • Ilmavirta M; Department of Neurology, Central Hospital Central Finland, Jyväskylä.
  • Nissilä M; Terveystalo Clinical Research, Turku, Finland.
  • Säkö E; Turku Headache Center, Turku, Finland.
  • Sumelahti ML; Terveystalo, Tampere, Finland.
  • Liukkonen J; Lääkärikeskus Ikioma, Mikkeli, Finland.
  • Sillanpää M; Departments of Child Neurology and General Practice, University of Turku, and Turku University Hospital, Turku, Finland.
  • Metsähonkala L; Epilepsy Unit for Children and Adolescents, Helsinki University Hospital, Helsinki, Finland.
  • Koskinen S; National Institute for Health and Welfare, Helsinki, Finland.
  • Lehtimäki T; Department of Clinical Chemistry, Fimlab Laboratories, Faculty of Medicine and Life Sciences, University of Tampere, Finland.
  • Raitakari O; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
  • Männikkö M; Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, Oulu, Finland.
  • Ran C; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Belin AC; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Jousilahti P; National Institute for Health and Welfare, Helsinki, Finland.
  • Anttila V; Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
  • Salomaa V; National Institute for Health and Welfare, Helsinki, Finland.
  • Artto V; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
  • Färkkilä M; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
  • Runz H; Merck Research Laboratories, Merck and Co., Kenilworth, NJ, USA.
  • Daly MJ; Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
  • Neale BM; Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ripatti S; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland; Public Health, Faculty of Medicine, University of Helsinki, Finland.
  • Kallela M; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
  • Wessman M; Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
  • Palotie A; Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland. Electronic address: aarno.palotie@helsinki.fi.
Neuron ; 98(4): 743-753.e4, 2018 05 16.
Article em En | MEDLINE | ID: mdl-29731251
ABSTRACT
Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71-1.81, p = 1.7 × 10-109) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25-1.38, p = 7.2 × 10-17). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Predisposição Genética para Doença / Enxaqueca com Aura / Enxaqueca sem Aura Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Predisposição Genética para Doença / Enxaqueca com Aura / Enxaqueca sem Aura Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article