TY - JOUR
T1 - A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine
AU - The International Headache Genetics Consortium
AU - The 23andMe Research Team
AU - Guo, Yanjun
AU - Rist, Pamela M.
AU - Daghlas, Iyas
AU - Giulianini, Franco
AU - Gormley, Padhraig
AU - Anttila, Verneri
AU - Winsvold, Bendik S.
AU - Palta, Priit
AU - Esko, Tonu
AU - Pers, Tune H.
AU - Farh, Kai How
AU - Cuenca-Leon, Ester
AU - Muona, Mikko
AU - Furlotte, Nicholas A.
AU - Kurth, Tobias
AU - Ingason, Andres
AU - McMahon, George
AU - Ligthart, Lannie
AU - Terwindt, Gisela M.
AU - Kallela, Mikko
AU - Freilinger, Tobias M.
AU - Ran, Caroline
AU - Gordon, Scott G.
AU - Stam, Anine H.
AU - Steinberg, Stacy
AU - Borck, Guntram
AU - Koiranen, Markku
AU - Quaye, Lydia
AU - Adams, Hieab H.H.
AU - Lehtimäki, Terho
AU - Sarin, Antti Pekka
AU - Wedenoja, Juho
AU - Hinds, David A.
AU - Buring, Julie E.
AU - Schürks, Markus
AU - Ridker, Paul M.
AU - Hrafnsdottir, Maria Gudlaug
AU - Stefansson, Hreinn
AU - Ring, Susan M.
AU - Hottenga, Jouke Jan
AU - Penninx, Brenda W.J.H.
AU - Färkkilä, Markus
AU - Artto, Ville
AU - Kaunisto, Mari
AU - Vepsäläinen, Salli
AU - Malik, Rainer
AU - Heath, Andrew C.
AU - Madden, Pamela A.F.
AU - Martin, Nicholas G.
AU - Montgomery, Grant W.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10−06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10−08), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15–1.25]/10 mmHg; P = 5.57 × 10−25) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg; P = 2.60 × 10−07) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg; P = 3.65 × 10−07). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.
AB - Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10−06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10−08), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15–1.25]/10 mmHg; P = 5.57 × 10−25) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg; P = 2.60 × 10−07) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg; P = 3.65 × 10−07). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.
UR - https://www.scopus.com/pages/publications/85087503588
U2 - 10.1038/s41467-020-17002-0
DO - 10.1038/s41467-020-17002-0
M3 - Article
C2 - 32632093
AN - SCOPUS:85087503588
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3368
ER -