TY - JOUR
T1 - Health effects associated with serum calcium concentrations
T2 - evidence from MR-PheWAS analysis in UK Biobank
AU - Zhou, A.
AU - Morris, H. A.
AU - Hyppönen, E.
N1 - Publisher Copyright:
© 2019, International Osteoporosis Foundation and National Osteoporosis Foundation.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Summary: We conducted a phenome-wide Mendelian randomization analysis (MR-PheWAS) to survey health effects associated with high normal serum calcium. We found causal evidence for conditions related to renal function, bone and joint health, and cardiovascular risk. These conditions collectively suggest that tissue calcification may be a key mechanism through which serum calcium influences health. Introduction: Calcium is essential for the normal functioning of the cardiovascular system, muscles, and nerves. In this MR-PheWAS study, we sought to capture the totality of health effects associated with high normal serum calcium. Methods: We used data from up to 337,535 UK Biobank participants, and tested for associations between calcium genetic score (calcium-GS) and 925 disease outcomes, with follow-up analyses using complementary MR methods. Results: Calcium-GS was robustly associated with serum calcium concentration (F statistics = 349). After multiple testing correction (P < 1.62E-4), we saw genetic evidence for an association between high serum calcium and urinary calculus (OR per 1 mg/dl 3.5, 95%CI 1.3–9.2), renal colic (9.1, 95%CI 2.5–33.5), and allergy/adverse effect of penicillin (2.2, 95%CI 1.5–3.3). Secondary analyses with independent replication from consortia meta-analyses suggested further effects on myocardial infarction and osteoarthrosis. Conclusion: We found causal evidence for effects of high normal serum calcium with conditions related to renal function, bone and joint health, and cardiovascular risk, which may collectively reflect influences on tissue calcification and immune function.
AB - Summary: We conducted a phenome-wide Mendelian randomization analysis (MR-PheWAS) to survey health effects associated with high normal serum calcium. We found causal evidence for conditions related to renal function, bone and joint health, and cardiovascular risk. These conditions collectively suggest that tissue calcification may be a key mechanism through which serum calcium influences health. Introduction: Calcium is essential for the normal functioning of the cardiovascular system, muscles, and nerves. In this MR-PheWAS study, we sought to capture the totality of health effects associated with high normal serum calcium. Methods: We used data from up to 337,535 UK Biobank participants, and tested for associations between calcium genetic score (calcium-GS) and 925 disease outcomes, with follow-up analyses using complementary MR methods. Results: Calcium-GS was robustly associated with serum calcium concentration (F statistics = 349). After multiple testing correction (P < 1.62E-4), we saw genetic evidence for an association between high serum calcium and urinary calculus (OR per 1 mg/dl 3.5, 95%CI 1.3–9.2), renal colic (9.1, 95%CI 2.5–33.5), and allergy/adverse effect of penicillin (2.2, 95%CI 1.5–3.3). Secondary analyses with independent replication from consortia meta-analyses suggested further effects on myocardial infarction and osteoarthrosis. Conclusion: We found causal evidence for effects of high normal serum calcium with conditions related to renal function, bone and joint health, and cardiovascular risk, which may collectively reflect influences on tissue calcification and immune function.
KW - Calcium genetic score
KW - Mendelian randomization
KW - Phenome-wide
KW - Serum calcium
UR - http://www.scopus.com/inward/record.url?scp=85070227782&partnerID=8YFLogxK
U2 - 10.1007/s00198-019-05118-z
DO - 10.1007/s00198-019-05118-z
M3 - Article
C2 - 31392400
AN - SCOPUS:85070227782
SN - 0937-941X
VL - 30
SP - 2343
EP - 2348
JO - Osteoporosis International
JF - Osteoporosis International
IS - 11
ER -