TY - JOUR
T1 - Association and genetic overlap between clinical chemistry tests and migraine
AU - Tanha, Hamzeh M.
AU - Martin, Nicholas G.
AU - Whitfield, John B.
AU - Nyholt, Dale R.
AU - The International Headache Genetics Consortium
AU - Ikram, M. Arfan
AU - Adams, Hieab
AU - Loehrer, Elizabeth
AU - Hofman, Bert
AU - van Duijn, C.M. (Cornelia)
AU - Uitterlinden, André
N1 - Publisher Copyright:
© International Headache Society 2021.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85117387254&partnerID=8YFLogxK
U2 - 10.1177/03331024211018131
DO - 10.1177/03331024211018131
M3 - Article
C2 - 34130515
AN - SCOPUS:85117387254
SN - 0333-1024
VL - 41
SP - 1208
EP - 1221
JO - Cephalalgia
JF - Cephalalgia
IS - 11-12
ER -
