TY - JOUR
T1 - Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families
AU - Gormley, Padhraig
AU - Kurki, Mitja I
AU - Hiekkala, Marjo Eveliina
AU - Veerapen, Kumar
AU - Häppölä, Paavo
AU - Mitchell, Adele A
AU - Lal, Dennis
AU - Palta, Priit
AU - Surakka, Ida
AU - Kaunisto, Mari Anneli
AU - Hämäläinen, Eija
AU - Vepsäläinen, Salli
AU - Havanka, Hannele
AU - Harno, Hanna
AU - Ilmavirta, Matti
AU - Nissilä, Markku
AU - Säkö, Erkki
AU - Sumelahti, Marja-Liisa
AU - Liukkonen, Jarmo
AU - Sillanpää, Matti
AU - Metsähonkala, Liisa
AU - Koskinen, Seppo
AU - Lehtimäki, Terho
AU - Raitakari, Olli
AU - Männikkö, Minna
AU - Ran, Caroline
AU - Belin, Andrea Carmine
AU - Jousilahti, Pekka
AU - Anttila, Verneri
AU - Salomaa, Veikko
AU - Artto, Ville
AU - Färkkilä, Markus
AU - Runz, Heiko
AU - Daly, Mark J
AU - Neale, Benjamin M
AU - Ripatti, Samuli
AU - Kallela, Mikko
AU - Wessman, Maija
AU - Palotie, Aarno
AU - Boomsma, D.I.
AU - Ligthart, L.
AU - Posthuma, Danielle
AU - 23Andme Research Team
N1 - Copyright © 2018 Elsevier Inc. All rights reserved.
PY - 2018/5/16
Y1 - 2018/5/16
N2 - 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. Gormley et al. use polygenic risk scores to show that common variation, captured by genome-wide association studies, in combination contributes to the aggregation of migraine in families. The results may have similar implications for other complex traits in general.
AB - 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. Gormley et al. use polygenic risk scores to show that common variation, captured by genome-wide association studies, in combination contributes to the aggregation of migraine in families. The results may have similar implications for other complex traits in general.
KW - disease aggregation
KW - familial aggregation
KW - families
KW - genome-wide association study
KW - GWAS
KW - hemiplegic migraine
KW - migraine
KW - migraine with aura
KW - polygenic risk score
KW - PRS
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U2 - 10.1016/j.neuron.2018.04.014
DO - 10.1016/j.neuron.2018.04.014
M3 - Article
C2 - 29731251
SN - 0896-6273
VL - 98
SP - 743-753.e4
JO - Neuron
JF - Neuron
IS - 4
ER -