Gormley, Padhraig ORCID: 0000-0002-8908-6968, Kurki, Mitja I., Hiekkala, Marjo Eveliina, Veerapen, Kumar, Happola, Paavo, Mitchell, Adele A., Lal, Dennis, Palta, Priit ORCID: 0000-0001-9320-7008, Surakka, Ida, Kaunisto, Mari Anneli, Hamalainen, Eija, Vepsalainen, Salli, Havanka, Hannele, Harno, Hanna ORCID: 0000-0002-6526-9436, Ilmavirta, Matti, Nissila, Markku, Sako, Erkki, Sumelahti, Marja-Liisa, Liukkonen, Jarmo, Sillanpaa, Matti, Metsahonkala, Liisa, Koskinen, Seppo, Lehtimaki, Terho, Raitakari, Olli, Mannikko, Minna, Ran, Caroline ORCID: 0000-0003-0239-9871, Belin, Andrea Carmine ORCID: 0000-0001-6668-3172, Jousilahti, Pekka, Anttila, Verneri, Salomaa, Veikko, Artto, Ville, Farkkila, Markus, Runz, Heiko, Daly, Mark J., Neale, Benjamin M., Ripatti, Samuli, Kallela, Mikko, Wessman, Maija and Palotie, Aarno (2018). Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families. Neuron, 98 (4). S. 743 - 758. CAMBRIDGE: CELL PRESS. ISSN 1097-4199

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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 significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71-1.81, p = 1.7 x 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 x 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gormley, PadhraigUNSPECIFIEDorcid.org/0000-0002-8908-6968UNSPECIFIED
Kurki, Mitja I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hiekkala, Marjo EveliinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Veerapen, KumarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Happola, PaavoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mitchell, Adele A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lal, DennisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palta, PriitUNSPECIFIEDorcid.org/0000-0001-9320-7008UNSPECIFIED
Surakka, IdaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaunisto, Mari AnneliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamalainen, EijaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vepsalainen, SalliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Havanka, HanneleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harno, HannaUNSPECIFIEDorcid.org/0000-0002-6526-9436UNSPECIFIED
Ilmavirta, MattiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nissila, MarkkuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sako, ErkkiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sumelahti, Marja-LiisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liukkonen, JarmoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sillanpaa, MattiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Metsahonkala, LiisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koskinen, SeppoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehtimaki, TerhoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raitakari, OlliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mannikko, MinnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ran, CarolineUNSPECIFIEDorcid.org/0000-0003-0239-9871UNSPECIFIED
Belin, Andrea CarmineUNSPECIFIEDorcid.org/0000-0001-6668-3172UNSPECIFIED
Jousilahti, PekkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anttila, VerneriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salomaa, VeikkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Artto, VilleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Farkkila, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Runz, HeikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daly, Mark J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neale, Benjamin M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ripatti, SamuliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kallela, MikkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wessman, MaijaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palotie, AarnoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-186390
DOI: 10.1016/j.neuron.2018.04.014
Journal or Publication Title: Neuron
Volume: 98
Number: 4
Page Range: S. 743 - 758
Date: 2018
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4199
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; 38 SUSCEPTIBILITY LOCI; HEMIPLEGIC MIGRAINE; CARDIOVASCULAR RISK; ANALYSES IDENTIFY; METAANALYSIS; RARE; MUTATIONS; SPECTRUM; FINLANDMultiple languages
NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18639

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