title: Genetic profiling and individualized assessment of fracture risk.
abstract: Osteoporosis and its consequence of fragility fracture impose a considerable demand on health-care services because fracture is associated with a series of adverse events, including re-fracture and mortality. One of the major priorities in osteoporosis care is the development of predictive models to identify individuals at high risk of fracture for early intervention and management. Existing predictive models include clinical factors and anthropometric characteristics but have not considered genetic variants in the prediction. Genome-wide association studies conducted in the past decade have identified several genetic variants relevant to fracture risk. These genetic variants are common in frequency but have very modest effect sizes. A remaining challenge is to use these genetic data to individualize fracture risk assessment on the basis of an individual's genetic risk profile. Empirical and simulation studies have shown that the usefulness of a single genetic variant for fracture risk assessment is very limited, but a profile of 50 genetic variants, each with odds ratio ranging from 1.02 to 1.15, could improve the accuracy of fracture prediction beyond that obtained by use of existing clinical risk factors. Thus, genetic profiling when integrated with existing risk assessment models could inform a more accurate prediction of fracture risk in an individual.
authors: Osteoporosis and Bone Biology Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia. t.nguyen@ garvan.org.au
authors: Tuan V
authors: TV
authors: Nguyen
authors: John A
authors: JA
authors: Eisman
mesh_terms: D015519:Bone Density; D005260:Female; D050723:Fractures, Bone / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010024:Osteoporosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D059467:Transcriptome / Q000235:genetics*
references: J Bone Miner Res. 2006 Feb;21(2):340-9
references: 16526127
references: J Orthop Trauma. 2005 Jul;19(6):396-400
references: 16003199
references: Osteoporos Int. 2008 Oct;19(10):1431-44
references: 18324342
references: J Clin Endocrinol Metab. 2005 Dec;90(12):6575-9
references: 16159929
references: Radiology. 1982 Apr;143(1):29-36
references: 7063747
references: Ann Intern Med. 2009 Oct 20;151(8):528-37
references: 19841454
references: Osteoporos Int. 2011 Dec;22(12):3079-80; author reply 3081-3
references: 21901474
references: Osteoporos Int. 2005 Jan;16(1):1-5
references: 15565349
references: Arch Intern Med. 2007 Aug 13-27;167(15):1641-7
references: 17698687
references: Nat Genet. 2012 Apr 15;44(5):491-501
references: 22504420
references: Nat Genet. 2009 Nov;41(11):1199-206
references: 19801982
references: Am J Epidemiol. 1998 Jan 1;147(1):3-16
references: 9440393
references: BMC Med Genet. 2007 Sep 19;8 Suppl 1:S14
references: 17903296
references: J Bone Miner Res. 2005 Nov;20(11):1921-8
references: 16234964
references: Bone. 2004 Nov;35(5):1029-37
references: 15542027
references: JAMA. 2007 Jan 24;297(4):387-94
references: 17244835
references: JAMA. 2009 Feb 4;301(5):513-21
references: 19190316
references: J Bone Miner Res. 1994 May;9(5):739-43
references: 8053404
references: PLoS Med. 2005 Aug;2(8):e124
references: 16060722
references: N Engl J Med. 1989 Mar 2;320(9):554-8
references: 2915666
references: J Bone Miner Res. 1998 Aug;13(8):1318-27
references: 9718201
references: Stat Med. 2008 Jan 30;27(2):157-72; discussion 207-12
references: 17569110
references: Lancet. 1999 Mar 13;353(9156):878-82
references: 10093980
references: J Bone Miner Res. 2007 Jun;22(6):781-8
references: 17352657
references: Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1193-8
references: 22223662
references: J Bone Miner Res. 2005 Jul;20(7):1185-94
references: 15940371
references: Calcif Tissue Int. 2009 Nov;85(5):379-88
references: 19789904
references: J Bone Miner Res. 2011 Feb;26(2):414-9
references: 20721935
references: J Bone Miner Res. 1994 Sep;9(9):1339-46
references: 7817817
references: J Clin Endocrinol Metab. 1994 Jun;78(6):1461-6
references: 8200950
references: Pharmacogenomics J. 2002;2(6):349-60
references: 12629506
references: Am J Epidemiol. 2004 May 1;159(9):882-90
references: 15105181
references: Nat Rev Genet. 2012 Jul 18;13(8):576-88
references: 22805710
references: Osteoporos Int. 2007 Aug;18(8):1109-17
references: 17370100
references: PLoS Genet. 2010 Feb 26;6(2):e1000864
references: 20195508
references: Osteoporos Int. 2003 Sep;14(9):701-15
references: 12904838
references: J Bone Miner Res. 2000 Jul;15(7):1243-52
references: 10893672
references: Nat Rev Genet. 2005 Feb;6(2):95-108
references: 15716906
references: J Bone Miner Res. 2007 Nov;22(11):1773-80
references: 17620052
references: Nature. 2007 Jun 7;447(7145):661-78
references: 17554300
references: Arch Intern Med. 1989 Nov;149(11):2445-8
references: 2818106
references: N Engl J Med. 1995 Mar 23;332(12):767-73
references: 7862179
references: Osteoporos Int. 2005 Aug;16(8):857-60
references: 15685396
references: Lancet. 2008 May 3;371(9623):1505-12
references: 18455228
references: J Clin Invest. 1987 Sep;80(3):706-10
references: 3624485
references: BMJ. 2011 Jun 07;342:d3520
references: 21652754
references: J Clin Endocrinol Metab. 2007 Mar;92(3):955-62
references: 17164302
references: Clin Chem. 2008 Jan;54(1):17-23
references: 18024533
references: Endocr Rev. 2010 Oct;31(5):629-62
references: 20431112
references: Am J Epidemiol. 2001 Mar 15;153(6):587-95
references: 11257067
references: Cancer Epidemiol Biomarkers Prev. 2010 Mar;19(3):655-65
references: 20160267
references: N Engl J Med. 2008 May 29;358(22):2355-65
references: 18445777
references: N Z Med J. 2011 Jun 24;124(1337):55-62
references: 21946878
references: BMJ. 1993 Oct 30;307(6912):1111-5
references: 8251809
references: J Clin Endocrinol Metab. 1999 Oct;84(10):3626-35
references: 10523006
references: Ann Intern Med. 1988 Dec 1;109(11):870-3
references: 3190041
references: Osteoporos Int. 2008 Apr;19(4):385-97
references: 18292978
references: Lancet. 2002 Jun 8;359(9322):2018-26
references: 12076571
references: Arch Intern Med. 2005 Sep 12;165(16):1825-30
references: 16157825