Dataset Information

Serum calcium and risk of migraine: a Mendelian randomization study.

ABSTRACT: Migraine affects ?14% of the world's population, though not all predisposing causal risk factors are known. We used electronic health records, genetic co-heritability analysis, and a two-sample Mendelian Randomization (MR) design to determine if elevated serum calcium levels were associated with risk of migraine headache. Co-morbidity was evaluated using electronic health records obtained from the PennOmics database comprising?>1 million patient entries. Genetic co-heritability and causality via MR was assessed using data from the International Headache Consortium (23,285 cases, 95,425 controls) and circulating serum calcium levels (39,400 subjects). We observed co-occurrence of migraine and hypercalcaemia ICD-9 diagnoses (OR?=?1.58, P?=?4 × 10-13), even after inclusion of additional risk factors for migraine (OR?=?1.23, P?=?2 × 10-3). Second, we observed co-heritability (rg?=?0.191, P?=?0.03) between serum calcium and migraine headache, indicating that these traits have a genetic basis in common. Finally, we found that elevation of serum calcium levels by 1?mg/dl resulting from our genetic score was associated with an increase in risk of migraine (OR?=?1.80, 95% CI: 1.31-2.46, P?=?2.5 × 10-4), evidence supporting a causal hypothesis. We also present multiple MR sensitivity analyses in support of this central finding. Our results provide evidence that hypercalcaemia is comorbid with migraine headache diagnoses, and that genetically elevated serum calcium over lifetime appears to increase risk for migraine. Further studies will be required to understand the biological mechanism, pathways, and clinical implication for risk management.

SUBMITTER: Yin P

PROVIDER: S-EPMC5409060 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Serum calcium and risk of migraine: a Mendelian randomization study.

Yin Peter P Anttila Verneri V Siewert Katherine M KM Palotie Aarno A Davey Smith George G Voight Benjamin F BF

Human molecular genetics 20170201 4

Migraine affects ∼14% of the world's population, though not all predisposing causal risk factors are known. We used electronic health records, genetic co-heritability analysis, and a two-sample Mendelian Randomization (MR) design to determine if elevated serum calcium levels were associated with risk of migraine headache. Co-morbidity was evaluated using electronic health records obtained from the PennOmics database comprising >1 million patient entries. Genetic co-heritability and causality via ...[more]

PMID: 28025330

Similar Datasets

Project description:BackgroundEvidence showed the supplementation of vitamin D might have beneficial effects for migraine patients. We aimed to investigate the causal effects of serum vitamin D levels on migraine risk using two-sample Mendelian randomization (MR) method.MethodsA total of 184 independent genetic instruments for serum vitamin D levels were selected from a study in 417,580 Europeans from UK biobank. Six variants from an independent study were obtained to perform replication analysis. Summary-level data for migraine were obtained from three studies with 48,975 migraine cases, 28,852 migraine cases and 10,536 migraine cases, respectively.ResultsThe estimated odds ratios (ORs) per standard deviation increase in circulating vitamin D levels based on the three migraine datasets were 0.948 (95% CI = 0.883-1.016, p = 0.133), 0.902 (95% confidence intervals [CI] = 0.825-0.986, p = 0.023), and 0.880 (95% CI = 0.786-0.984, p = 0.025), respectively. Using pooled migraine summary data with no sample overlap, MR analysis showed per standard deviation increase in circulating vitamin D levels was significantly associated with a decreased migraine risk (OR = 0.916, 95% CI = 0.859-0.977, p = 0.008). Multivariable MR analyses, sensitivity analyses and replication analysis confirmed the association. MR analyses showed similar estimates for migraine with aura and migraine without aura but with wider 95% CIs. Mediation analysis showed the effect of vitamin D on migraine risk via pathway of serum calcium was corresponding to an OR of 1.003 (95% CI = 1.001-1.005) and a proportion mediated of 3.42%. The reverse MR analysis showed migraine might not affect vitamin D levels.ConclusionThis two-sample MR study showed genetically determined increased circulating vitamin D levels are associated with decreased migraine risk. The effect seems consistent across different migraine subtypes. In addition, the role of serum calcium in mediating the association between vitamin D and migraine is negligible. Future large well-designed randomized trials are warranted to assess the effects of vitamin D supplementation for migraine patients, especially in those with vitamin D deficiency.

Dataset Information

Serum calcium and risk of migraine: a Mendelian randomization study.

Publications

Serum calcium and risk of migraine: a Mendelian randomization study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets