Serum calcium and risk of migraine : a Mendelian randomization study

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Yin , P , Anttila , V , Siewert , K M , Palotie , A , Smith , G D & Voight , B F 2017 , ' Serum calcium and risk of migraine : a Mendelian randomization study ' , Human Molecular Genetics , vol. 26 , no. 4 , pp. 820-828 .

Title: Serum calcium and risk of migraine : a Mendelian randomization study
Author: Yin, Peter; Anttila, Verneri; Siewert, Katherine M.; Palotie, Aarno; Smith, George Davey; Voight, Benjamin F.
Contributor organization: Aarno Palotie / Principal Investigator
University of Helsinki
Institute for Molecular Medicine Finland
Genomics of Neurological and Neuropsychiatric Disorders
Date: 2017-02-15
Language: eng
Number of pages: 9
Belongs to series: Human Molecular Genetics
ISSN: 0964-6906
Abstract: Migraine affects similar to 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-sampleMendelian 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 x 10-(13)), even after inclusion of additional risk factors for migraine (OR = 1.23, P = 2 x 10 -(3)). Second, we observed co-heritability (r(g) =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 x 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 biologicalmechanism, pathways, and clinical implication for riskmanagement.
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion

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