Article Text

PDF
Original article
Meta-analysis of genome-wide studies identifies MEF2C SNPs associated with bone mineral density at forearm
  1. Hou-Feng Zheng1,
  2. Emma L Duncan2,3,
  3. Laura M Yerges-Armstrong4,
  4. Joel Eriksson5,
  5. Ulrica Bergström6,
  6. Paul J Leo2,
  7. William D Leslie7,
  8. David Goltzman8,
  9. John Blangero9,
  10. David A Hanley10,
  11. Melanie A Carless11,
  12. Elizabeth A Streeten4,11,
  13. Mattias Lorentzon5,
  14. Matthew A Brown2,
  15. Tim D Spector12,
  16. Ulrika Pettersson-Kymmer13,14,
  17. Claes Ohlsson5,
  18. Braxton D Mitchell4,11,
  19. J Brent Richards1,12
  1. 1Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
  2. 2Human Genetics Group, The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Queensland, Australia
  3. 3Department of Endocrinology, Royal Brisbane and Women's Hospital, Brisbane, Australia
  4. 4Department of Medicine University of Maryland School of Medicine, Baltimore, Maryland, USA
  5. 5Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  6. 6Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden
  7. 7Department of Internal Medicine, University of Manitoba, Winnipeg, Canada
  8. 8Department of Medicine, McGill University, Montreal, Canada
  9. 9Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, USA
  10. 10Department of Medicine, Calgary, AB, Canada
  11. 11Geriatric Research and Education Clinical Center (GRECC), Veterans Administration Medical Center, Baltimore, Maryland, USA
  12. 12Twin Research and Genetic Epidemiology, King's College London, London, UK
  13. 13Department of Pharmacology and Neuroscience, Umeå University, Umeå, Sweden
  14. 14Department of Public Health and Clinical Medicine, Umeå Unviersity, Umeå, Sweden
  1. Correspondence to Dr Hou-Feng Zheng or Dr J Brent Richards, Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Lady Davis Institute, Jewish General Hospital, McGill University, 3755, Côte Ste-Catherine Road, Montreal, Québec H3T 1E2, Canada; hou.zheng{at}mail.mcgill.ca and brent.richards{at}mcgill.ca

Abstract

Background Forearm fractures affect 1.7 million individuals worldwide each year and most occur earlier in life than hip fractures. While the heritability of forearm bone mineral density (BMD) and fracture is high, their genetic determinants are largely unknown.

Aim To identify genetic variants associated with forearm BMD and forearm fractures.

Methods BMD at distal radius, measured by dual-energy x-ray absorptiometry, was tested for association with common genetic variants. We conducted a meta-analysis of genome-wide association studies for BMD in 5866 subjects of European descent and then selected the variants for replication in 715 Mexican American samples. Gene-based association was carried out to supplement the single-nucleotide polymorphism (SNP) association test. We then tested the BMD-associated SNPs for association with forearm fracture in 2023 cases and 3740 controls.

Results We found that five SNPs in the introns of MEF2C were associated with forearm BMD at a genome-wide significance level (p<5×10–8) in meta-analysis (lead SNP, rs11951031[T] −0.20 SDs per allele, p=9.01×10–9). The gene-based association test suggested an association between MEF2C and forearm BMD (p=0.003). The association between MEF2C variants and risk of fracture did not achieve statistical significance (SNP rs12521522[A]: OR=1.14 (95% CI 0.92 to 1.35), p=0.14). Meta-analysis also revealed two genome-wide suggestive loci at CTNNA2 and 6q23.2.

Conclusions These findings demonstrate that variants at MEF2C were associated with forearm BMD, implicating this gene in the determination of BMD at forearm.

  • Complex traits
  • Genome-wide
  • Genetic epidemiology

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.