title: No causal effect of serum urate on bone-related outcomes among a population of postmenopausal women and elderly men of Chinese Han ethnicity--a Mendelian randomization study.
abstract: CONCLUSIONS
  We conducted a Mendelian randomization analysis to assess the effect of serum uric acid on bone-related outcomes using a weighted urate transporter genetic risk score as the instrumental variable. The results showed no significance. Our study identified no evidence of a causal role between uric acid and bone-related outcomes.
  
  
  BACKGROUND
  Observational studies have associated elevated levels of serum uric acid (SUA) with increasing bone mineral density (BMD) and a lowered prevalence of osteoporotic fractures (OFs) in postmenopausal women and elderly men. However, due to unmeasured confounding variables, these observational studies have not provided insight into the causal relationship between SUA and bone-related outcomes. Our aim was to evaluate the effect of SUA on bone-related outcomes using Mendelian randomization.
  
  
  METHODS
  We recruited 1322 Chinese Han individuals (214 elderly men and 1108 postmenopausal women) from the Shanghai area in China. Mendelian randomization using a two-stage least-squares regression method was conducted with SUA as the exposure variable, a weighted urate transporter genetic risk score as the instrumental variable, and all-site BMD, bone turnover markers, and levels of 25-hydroxyvitamin D3 [25(OH)D], serum calcium (Ca), serum phosphorus (P), and parathyroid hormone (PTH) as outcome variables.
  
  
  RESULTS
  Strong associations between SUA and bone-related outcomes were observed in an ordinary observational analysis (lumbar spine: beta = 0.122, p < 0.0001; hip: beta = 0.104, p < 0.0001; femoral neck: beta = 0.108, p < 0.0001). However, the Mendelian randomization analysis showed no evidence for a causal association of SUA with BMD (lumbar spine: beta = 0.385, p = 0.257; hip: beta = 0.191, p = 0.499; femoral neck: beta = 0.194, p = 0.533). Similar results were found between SUA and other bone-related phenotypes.
  
  
  CONCLUSIONS
  Our study identified no evidence of a causal role between SUA and bone-related outcomes, although strong associations in an observational analysis were observed in a population of postmenopausal women and elderly men.
authors.affiliation: Geriatric Department of Ningbo First Hospital, 59 Liu-Ting St, Ningbo, 315010, China.
authors.forename: A
authors.initials: A
authors.lastname: Xiong
authors.affiliation: Geriatric Department of Ningbo First Hospital, 59 Liu-Ting St, Ningbo, 315010, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Rd, Shanghai, 200233, China.
authors.forename: J
authors.initials: J
authors.lastname: He
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Rd, Shanghai, 200233, China.
authors.forename: W
authors.initials: W
authors.lastname: Fu
authors.affiliation: Geriatric Department of Ningbo First Hospital, 59 Liu-Ting St, Ningbo, 315010, China. yujingbo@medmail.com.cn.
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Rd, Shanghai, 200233, China. zzl2002@medmail.com.cn.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000235:genetics* / Q000502:physiology; D005260:Female; D005272:Femur Neck / Q000502:physiology; D005787:Gene Frequency; D006621:Hip Joint / Q000502:physiology; D006801:Humans; D008159:Lumbar Vertebrae / Q000502:physiology; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000097:blood; D014527:Uric Acid / Q000097:blood*
chemical_list: D015415:Biomarkers; D014527:Uric Acid
keywords: Bone mineral density; Causal effect; Genetic; Mendelian randomization; Uric acid