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 - Funding Information:
This research has been conducted using the UK Biobank Resource under Application Number 29273. We would like to thank the participants and researchers from the UK Biobank, 23andMe, Inc., International Headache Genetics Consortium (IHGC), MEGASTROKE, CARDIoGRAM, and International Consortium of Blood Pressure-Genome Wide Association Studies (ICBP) who contributed or collected data. Daniel I. Chasman is funded by US National Institutes of Health and US National Institute of Neurological Disorders and Stroke (R21NS09296 and R21NS104398). Pamela M. Rist is funded by K01 HL128791. The MEGASTROKE project received funding from sources specified at http://www.megastroke.org/acknowledgments.html.
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 - http://www.scopus.com/inward/record.url?scp=85087503588&partnerID=8YFLogxK
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 -