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Genome-wide Association Studies for Osteoporosis: A 2013 Update

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초록

In the past few years, the bone field has witnessed great advances in genome-wide as-sociation studies (GWASs) of osteoporosis, with a number of promising genes identified. In particular, meta-analysis of GWASs, aimed at increasing the power of studies by com-bining the results from different study populations, have led to the identification of nov-el associations that would not otherwise have been identified in individual GWASs. Re-cently, the first whole genome sequencing study for osteoporosis and fractures waspublished, reporting a novel rare nonsense mutation. This review summarizes the im-portant and representative findings published by December 2013. Comments are madeon the notable findings and representative studies for their potential influence and im-plications on our present understanding of the genetics of osteoporosis. Potential limi-tations of GWASs and their meta-analyses are evaluated, with an emphasis on under-standing the reasons for inconsistent results between different studies and clarificationof misinterpretation of GWAS meta-analysis results. Implications and challenges ofGWAS are also discussed, including the need for multi- and inter-disciplinary studies.

Abstract

In the past few years, the bone field has witnessed great advances in genome-wide as-sociation studies (GWASs) of osteoporosis, with a number of promising genes identified. In particular, meta-analysis of GWASs, aimed at increasing the power of studies by com-bining the results from different study populations, have led to the identification of nov-el associations that would not otherwise have been identified in individual GWASs. Re-cently, the first whole genome sequencing study for osteoporosis and fractures waspublished, reporting a novel rare nonsense mutation. This review summarizes the im-portant and representative findings published by December 2013. Comments are madeon the notable findings and representative studies for their potential influence and im-plications on our present understanding of the genetics of osteoporosis. Potential limi-tations of GWASs and their meta-analyses are evaluated, with an emphasis on under-standing the reasons for inconsistent results between different studies and clarificationof misinterpretation of GWAS meta-analysis results. Implications and challenges ofGWAS are also discussed, including the need for multi- and inter-disciplinary studies.

참고문헌 (72)

  1. Cummings SR., "Epidemiology of osteoporosis and osteoporotic fractures", Epidemiol Rev., 7, pp.178~208 (1985)
  2. Cummings SR., "Epidemiology and outcomes of osteoporotic fractures", Lancet., 359, pp.1761~1767 (2002)
  3. Ralston SH., "Genetics of osteoporosis", Rev Endocr Metab Disord., 2, pp.13~21 (2001)
  4. Recker RR., "Role of genetics in osteoporosis", Endocrine., 17, pp.55~66 (2002)
  5. Xu XH., "Molecular genetic studies of gene identification for osteoporosis: the 2009 update", Endocr Rev., 31, pp.447~505 (2010)
  6. Livshits G., "Genetics of bone mineral density: evidence for a major pleiotropic effect from an intercontinental study", J Bone Miner Res., 19, pp.914~923 (2004)
  7. Deng HW., "Relevance of the genes for bone mass variation to susceptibility to osteoporotic fractures and its implications to gene search for complex human diseases", Genet Epidemiol., 22, pp.12~25 (2002)
  8. Michaëlsson K., "Genetic liability to fractures in the elderly", Arch Intern Med., 165, pp.1825~1830 (2005)
  9. Styrkarsdottir U., "Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits", Nature., 497, pp.517~520 (2013)
  10. Richards JB., "Genetics of osteoporosis from genome-wide association studies: advances and challenges", Nat Rev Genet., 13, pp.576~588 (2012)
  11. Rivadeneira F., "Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies", Nat Genet., 41, pp.1199~1206 (2009)
  12. Estrada K., "Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture", Nat Genet., 44, pp.491~501 (2012)
  13. Deng HW., "Genetic determination of Colles' fracture and differential bone mass in women with and without Colles' fracture", J Bone Miner Res., 15, pp.1243~1252 (2000)
  14. Richards JB., "Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture", Ann Intern Med., 151, pp.528~537 (2009)
  15. Fink HA., "Differences in site-specific fracture risk among older women with discordant results for osteoporosis at hip and spine: study of osteoporotic fractures", J Clin Densitom., 11, pp.250~259 (2008)
  16. Augat P., "Prediction of fracture load at different skeletal sites by geometric properties of the cortical shell", J Bone Miner Res., 11, pp.1356~1363 (1996)
  17. Koller DL., "Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women", J Bone Miner Res., 28, pp.547~558 (2013)
  18. Zhang L., "Multistage genome-wide association meta-analyses identified two new loci for bone mineral density", Hum Mol Genet., 23, pp.1923~1933 (2014)
  19. Paternoster L., "Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure", PLoS Genet., 9, pp.e1003247~ (2013)
  20. Lee DC., "Limitations of peripheral quantitative computed tomography metaphyseal bone density measurements", J Clin Endocrinol Metab., 92, pp.4248~4253 (2007)
  21. Adams JE., "Quantitative computed tomography", Eur J Radiol., 71, pp.415~424 (2009)
  22. Engelke K., "Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD Official Positions", J Clin Densitom, 11, pp.123~162 (2008)
  23. Richards JB., "Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study", Lancet., 371, pp.1505~1512 (2008)
  24. Styrkarsdottir U., "Multiple genetic loci for bone mineral density and fractures", N Engl J Med., 358, pp.2355~2365 (2008)
  25. Deng HW., "QTL fine mapping, in extreme samples of finite populations, for complex traits with familial correlation due to polygenes", Am J Hum Genet., 67, pp.259~262 (2000)
  26. Duncan EL., "Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk", PLoS Genet., 7, pp.e100137~ (2011)
  27. Hsu YH., "An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits", PLoS Genet., 6, pp.e100977~ (2010)
  28. Deng FY., "Peripheral blood monocyte-expressed ANXA2 gene is involved in pathogenesis of osteoporosis in humans", Mol Cell Proteomics., 10(M111), pp.011700~ (2011)
  29. Liu YZ., "A novel pathophysiological mechanism for osteoporosis suggested by an in vivo gene expression study of circulating monocytes", J Biol Chem., 280, pp.29011~29016 (2005)
  30. Xiong DH., "Genome-wide association and follow-up replication studies identified ADAMTS18 and TGFBR3 as bone mass candidate genes in different ethnic groups", Am J Hum Genet., 84, pp.388~398 (2009)
  31. Koller DL., "Genome-wide association study of bone mineral density in premenopausal European-American women and replication in African-American women", J Clin Endocrinol Metab., 95, pp.1802~1809 (2010)
  32. Timpson NJ., "Common variants in the region around Osterix are associated with bone mineral density and growth in childhood", Hum Mol Genet., 18, pp.1510~1517 (2009)
  33. Medina-Gomez C., "Meta-analysis of genome-wide scans for total body BMD in children and adults reveals allelic heterogeneity and age-specific effects at the WNT16 locus", PLoS Genet., 8, pp.e1002718~ (2012)
  34. Zheng HF., "WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk", PLoS Genet., 8, pp.e1002745~ (2012)
  35. Nguyen TV., "Genetic profiling and individualized assessment of fracture risk", Nat Rev Endocrinol., 9, pp.153~161 (2013)
  36. Chen Y., "Choice of study phenotype in osteoporosis genetic research", J Bone Miner Metab., 27, pp.121~126 (2009)
  37. Guo Y., "Genome-wide association study identifies ALDH7A1 as a novel susceptibility gene for osteoporosis", PLoS Genet., 6, pp.e1000806~ (2010)
  38. Hwang JY, "Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture", J Med Genet., 50, pp.212~219 (2013)
  39. Rosen CJ., "Primer on the metabolic bone diseases and disorders of mineral metabolism" (2008), American Society for Bone and Mineral Research
  40. Melton LJ, "The prevalence of osteoporosis: gender and racial comparison", Calcif Tissue Int, 69, pp.179~181 (2001)
  41. McCarroll SA., "Copy-number variation and association studies of human disease", Nat Genet., 39, pp.S37~42 (2007)
  42. Yang TL., "Genome-wide copy-number-variation study identified a susceptibility gene, UGT2B17, for osteoporosis", Am J Hum Genet., 83, pp.663~674 (2008)
  43. Oei L., "A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus", J Med Genet., 51, pp.122~131 (2014)
  44. Zhang L., "Pathway-based genome-wide association analysis identified the importance of regulation-of-autophagy pathway for ultradistal radius BMD", J Bone Miner Res., 25, pp.1572~1580 (2010)
  45. Bohensky J., "PIM-2 is an independent regulator of chondrocyte survival and autophagy in the epiphyseal growth plate", J Cell Physiol., 213, pp.246~251 (2007)
  46. Zhang YP., "Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures", PLoS One., 6, pp.e21835~ (2011)
  47. Wang K., "Pathway-based approaches for analysis of genomewide association studies", Am J Hum Genet., 81, pp.1278~1283 (2007)
  48. Liu YZ., "Powerful bivariate genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males", PLoS One., 4, pp.e6827~ (2009)
  49. Gorlov IP., "Shifting paradigm of association studies: value of rare single-nucleotide polymorphisms", Am J Hum Genet., 82, pp.100~112 (2008)
  50. Bodmer W., "Common and rare variants in multifactorial susceptibility to common diseases", Nat Genet., 40, pp.695~701 (2008)
  51. Cirulli ET., "Uncovering the roles of rare variants in common disease through whole-genome sequencing", Nat Rev Genet., 11, pp.415~425 (2010)
  52. Liu YJ., "On genome-wide association studies and their meta-analyses: lessons learned from osteoporosis studies", J Clin Endocrinol Metab., 98, pp.E1278~1282 (2013)
  53. Pei YF., "On individual genome-wide association studies and their meta-analysis", Hum Genet., 133, pp.265~279 (2014)
  54. Liu YJ., "Molecular genetic studies of gene identification for osteoporosis: a 2004 update", J Bone Miner Res., 21, pp.1511~1535 (2006)
  55. Liu YZ., "Molecular studies of identification of genes for osteoporosis: the 2002 update", J Endocrinol., 177, pp.147~196 (2003)
  56. Abecasis GR., "A map of human genome variation from population-scale sequencing", Nature., 467, pp.1061~1073 (2010)
  57. Mills RE., "Mapping copy number variation by population-scale genome sequencing", Nature., 470, pp.59~65 (2011)
  58. Manolio TA., "Finding the missing heritability of complex diseases", Nature., 461, pp.747~753 (2009)
  59. Rodenhiser D., "Epigenetics and human disease: translating basic biology into clinical applications", CMAJ., 174, pp.341~348 (2006)
  60. Teitelbaum SL., "RANKing c-Jun in osteoclast development", J Clin Invest., 114, pp.463~465 (2004)
  61. Jimi E., "Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function", J Immunol., 163, pp.434~442 (1999)
  62. Heinrich PC., "Principles of interleukin (IL)-6-type cytokine signalling and its regulation", Biochem J., 374, pp.1~20 (2003)
  63. Ihnatko R., "TNF signaling: early events and phosphorylation", Gen Physiol Biophys., 26, pp.159~167 (2007)
  64. Milani R., "Phosphoproteome reveals an atlas of protein signaling networks during osteoblast adhesion", J Cell Biochem., 109, pp.957~966 (2010)
  65. Deng FY., "Proteomic analysis of circulating monocytes in Chinese premenopausal females with extremely discordant bone mineral density", Proteomics., 8, pp.4259~4272 (2008)
  66. Farber CR., "Systems-level analysis of genome-wide association data", G3 (Bethesda)., 3, pp.119~129 (2013)
  67. Farber CR., "Systems genetics: a novel approach to dissect the genetic basis of osteoporosis", Curr Osteoporos Rep., 10, pp.228~235 (2012)
  68. Calabrese G., "Systems genetic analysis of osteoblast-lineage cells", PLoS Genet., 8, pp.e1003150~ (2012)
  69. Deng FY., "An integrative study ascertained SOD2 as a susceptibility gene for osteoporosis in Chinese", J Bone Miner Res., 26, pp.2695~2701 (2011)
  70. Styrkarsdottir U., "European bone mineral density loci are also associated with BMD in East-Asian populations", PLoS One., 5, pp.e13217~ (2010)
  71. Kung AW., "Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies", Am J Hum Genet., 86, pp.229~239 (2010)
  72. Styrkarsdottir U., "New sequence variants associated with bone mineral density", Nat Genet., 41, pp.15~17 (2009)

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