Assessing the associations of blood metabolites with osteoporosis: a Mendelian randomization study.

Assessing the associations of blood metabolites with osteoporosis: a Mendelian randomization study.

J Clin Endocrinol Metab. 2018 Mar 01;:

Authors: Liu L, Wen Y, Zhang L, Xu P, Liang X, Du Y, Li P, He A, Fan Q, Hao J, Wang W, Guo X, Shen H, Tian Q, Zhang F, Deng HW

Abstract
Context: Osteoporosis is a metabolic bone disease. The impact of blood metabolites on the development of osteoporosis remains elusive now.
Objective: To explore the relationship between blood metabolites and osteoporosis.
Design and Methods: We used 2,286 unrelated Caucasian subjects as discovery samples and 3,143 unrelated Caucasian subjects from the Framingham heart study (FHS) as replication samples. Bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry. Genome-wide SNP genotyping was performed using Affymetrix Human SNP Array 6.0 (for discovery samples) and Affymetrix SNP 500K and 50K array (for FHS replication samples). The SNP sets significantly associated with blood metabolites were obtained from a published whole-genome sequencing study. For each subject, the genetic risk score (GRS) of metabolite was calculated from the genotype data of metabolite associated SNP sets. Pearson correlation analysis was conducted to evaluate the potential impact of blood metabolites on the variations bone phenotypes. 10,000 permutations were conducted to calculate the empirical P value and false discovery rate (FDR).
Results: 481 blood metabolites were analyzed in this study. We identified multiple blood metabolites associated with hip BMD, such as 1,5-anhydroglucitol(1,5-AG) (Pdiscovery < 0.0001, Preplication = 0.0361), inosine (Pdiscovery = 0.0018, Preplication = 0.0256), theophylline (Pdiscovery = 0.0048, Preplication = 0.0433, gamma-glutamylmethionine (Pdiscovery = 0.0047, Preplication = 0.0471), 1-linoleoyl-2-arachidonoyl-GPC (18:2/20:4n6) (Pdiscovery = 0.0018, Preplication=0.0390) and X-12127 (Pdiscovery = 0.0002, Preplication = 0.0249).
Conclusions: Our results suggest the modest impact of blood metabolites on the variations of BMD, and identified several candidate blood metabolites for osteoporosis.

PMID: 29506141 [PubMed - as supplied by publisher]

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