Association and genetic overlap between clinical chemistry tests and migraine

Hamzeh M. Tanha, Nicholas G. Martin, John B. Whitfield, Dale R. Nyholt, Padhraig Gormley, Verneri Anttila, Bendik S. Winsvold, Priit Palta, Tonu Esko, Tune H. Pers, Kai How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A. Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M. Terwindt, Mikko KallelaTobias M. Freilinger, Caroline Ran, Scott G. Gordon, Anine H. Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H.H. Adams, Terho Lehtim€aki, Antti Pekka Sarin, Juho Wedenoja, David A. Hinds, Julie E. Buring, Markus Schurks, Paul M. Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M. Ring, Jouke Jan Hottenga, Brenda WJH Penninx, Markus F€arkkil€a, Ville Artto, Mari Kaunisto, Salli Veps€al€ainen, Rainer Malik, Andrew C. Heath, Pamela AF Madden, Nicholas G. Martin, Grant W. Montgomery, Mitja I. Kurki, Mart Kals, Reedik M€agi, Kalle P€arn, Eija H€am€al€ainen, Hailiang Huang, Andrea E. Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H. Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G. Eriksson, Veikko Salomaa, Kauko Heikkil€a, Elizabeth Loehrer, Andre G. Uitterlinden, Albert Hofman, Cornelia M. van Duijn, Lynn Cherkas, Linda M. Pedersen, Audun Stubhaug, Christopher S. Nielsen, Minna M€annikk€o, Evelin Mihailov, Lili Milani, Hartmut G€obel, Ann Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J. Aromaa, Olli Raitakari, M. Arfan Ikram, Tim Spector, Marjo Riitta J€arvelin, Andres Metspalu, Christian Kubisch, David P. Strachan, Michel D. Ferrari, Andrea C. Belin, Martin Dichgans, Maija Wessman, Arn M.J.M. van den Maagdenberg, John Anker Zwart, Dorret I. Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J. Daly, Benjamin M. Neale, Jes Olesen, Daniel I. Chasman, Aarno Palotie, Aarno Palotie

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Introduction: In this paper, we studied several serum clinical chemistry tests of cardiovascular disease (CVD), iron deficiency anemia, liver and kidney disorders in migraine. Methods: We first explored the association of 22 clinical chemistry tests with migraine risk in 697 migraine patients and 2722 controls. To validate and interpret association findings, cross-trait genetic analyses were conducted utilising genome-wide association study (GWAS) data comprising 23,986 to 452,264 individuals. Results: Significant associations with migraine risk were identified for biomarkers of CVD risk, iron deficiency and liver dysfunction (odds ratios = 0.86–1.21; 1 × 10−4 < p < 3 × 10−2). Results from cross-trait genetic analyses corroborate the significant biomarker associations and indicate their relationship with migraine is more consistent with biological pleiotropy than causality. For example, association and genetic overlap between a lower level of HDL-C and increased migraine risk are due to shared biology rather than a causal relationship. Furthermore, additional genetic analyses revealed shared genetics among migraine, the clinical chemistry tests, and heart problems and iron deficiency anemia, but not liver disease. Conclusions: These findings highlight common biological mechanisms underlying migraine, heart problems and iron deficiency anemia and provide support for their investigation in the development of novel therapeutic and dietary interventions.

Original languageEnglish
Pages (from-to)1208-1221
Number of pages14
JournalCephalalgia
Volume41
Issue number11-12
DOIs
StatePublished - Oct 2021

Keywords

  • Biochemistry tests
  • Mendelian randomisation
  • SNP-based genetic overlap
  • gene-based genetic overlap
  • genetic correlation

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