Relationship Between Serum Amino Acid Levels and Bone Mineral Density: A Mendelian Randomization Study.

Zhiyong Cui,Baichuan He,Yun Tian,Hui Feng,Jinyao He

doi:10.3389/fendo.2021.763538

Abstract

BackgroundThis study aimed to explore the association between serum amino acids (AAs) levels and bone mineral density (BMD).MethodsWe performed a two-sample Mendelian randomization (MR) analysis to analyze the associations between the levels of eight AAs and BMD values by using summary-level genome-wide association study (GWAS) data. We applied the MR Steiger filtering method and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test to check for and remove single nucleotide polymorphisms (SNPs) that were horizontally pleiotropic. The associations were estimated with the inverse variance weighted (IVW), MR-Egger, weighted median and MR Robust Adjusted Profile Score (MR.RAPS) methods.ResultsOur study found that genetically increased isoleucine (Ile) [IVW: effect = 0.1601, 95% confidence interval (CI) = 0.0604 ~ 0.2597, p = 0.0016] and valine (Val) levels (IVW: effect = 0.0953, 95% CI = 0.0251 ~ 0.1655, p = 0.0078) were positively associated with total body BMD (TB-BMD). The results also revealed that genetically increased tyrosine (Tyr) levels were negatively associated with TB-BMD (IVW: effect = -0.1091, 95% CI = -0.1863 ~ -0.0320, p = 0.0055).ConclusionsIn this study, associations between serum AA levels and BMD were established. These findings underscore the important role that serum AAs play in the development of osteoporosis and provide evidence that osteoporosis can be prevented and treated by the intake of certain AAs.

Highlights

Osteoporosis is the most common bone disease, and it is characterized by low bone mass, bone tissue deterioration and bone structure disruption [1]
We only focused on the particular set of amino acids (AAs) and extracted summary statistics about eight single AAs, namely, alanine (Ala), glutamine (Gln), histidine (His), isoleucine (Ile), leucine (Leu), phenylalanine (Phe), tyrosine (Tyr) and valine (Val), because we wanted to investigate whether AA metabolism could be associated with bone mineral density (BMD) values
We removed the palindromic single nucleotide polymorphisms (SNPs) when harmonizing the effect of instrumental variables (IVs) and excluded the SNPs with false causal direction identified by the Mendelian randomization (MR) Steiger filtering

Summary

Introduction

Osteoporosis is the most common bone disease, and it is characterized by low bone mass, bone tissue deterioration and bone structure disruption [1]. Osteoporosis is the reason for fragility fractures, and the most common fracture sites are the spine, hip and distal forearm. The one-year estimated mortality of hip fractures in mainland China is 13.96% [2]. Osteoporosis is a Relationship Between AAs and BMD major threat to an enormous number of people and exacts a terrible toll on elderly adults, who constitute a rapidly growing population in the world. The measurement of bone mineral density (BMD) has been proven to be an effective method for diagnosing osteoporosis and assessing the risk of fragility fracture [3]. Osteoporosis is an important and common public health problem, the mechanisms and risk factors underlying osteoporosis and BMD are still poorly understood. This study aimed to explore the association between serum amino acids (AAs) levels and bone mineral density (BMD)

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