Association and genetic overlap between clinical chemistry tests and migraine
Tanha HM., Martin NG., Whitfield JB., Nyholt DR., Gormley P., Anttila V., Winsvold BS., Palta P., Esko T., Pers TH., Farh KH., Cuenca-Leon E., Muona M., Furlotte NA., Kurth T., Ingason A., McMahon G., Ligthart L., Terwindt GM., Kallela M., Freilinger TM., Ran C., Gordon SG., Stam AH., Steinberg S., Borck G., Koiranen M., Quaye L., Adams HHH., Lehtim€aki T., Sarin AP., Wedenoja J., Hinds DA., Buring JE., Schurks M., Ridker PM., Hrafnsdottir MG., Stefansson H., Ring SM., Hottenga JJ., Penninx BW., F€arkkil€a M., Artto V., Kaunisto M., Veps€al€ainen S., Malik R., Heath AC., Madden PA., Martin NG., Montgomery GW., Kurki MI., Kals M., M€agi R., P€arn K., H€am€al€ainen E., Huang H., Byrnes AE., Franke L., Huang J., Stergiakouli E., Lee PH., Sandor C., Webber C., Cader Z., Muller-Myhsok B., Schreiber S., Meitinger T., Eriksson JG., Salomaa V., Heikkil€a K., Loehrer E., Uitterlinden AG., Hofman A., van Duijn CM., Cherkas L., Pedersen LM., Stubhaug A., Nielsen CS., M€annikk€o M., Mihailov E., Milani L., G€obel H., Esserlind AL., Christensen AF., Hansen TF., Werge T., Kaprio J., Aromaa AJ., Raitakari O., Ikram MA., Spector T., J€arvelin MR., Metspalu A., Kubisch C., Strachan DP., Ferrari MD., Belin AC., Dichgans M., Wessman M., van den Maagdenberg AMJM.
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.