Replication of Caucasian Loci Associated with Osteoporosis-related Traits in East Asians
0
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background: Most reported genome-wide association studies (GWAS) seeking to identify the loci of osteoporosis-related traits have involved Caucasian populations. We aimed to identify the single nucleotide polymorphisms (SNPs) of osteoporosis-related traits among East Asian populations from the bone mineral density (BMD)-related loci of an earlier GWAS meta-analysis. Methods: A total of 95 SNPs, identified at the discovery stage of the largest GWAS meta-analysis of BMD, were tested to determine associations with osteoporosis-related traits (BMD, osteoporosis, or fracture) in Korean subjects (n=1,269). The identified SNPs of osteoporosis-related traits in Korean subjects were included in the replication analysis using Chinese (n=2,327) and Japanese (n=768) cohorts. Results: A total of 17 SNPs were associated with low BMD in Korean subjects. Specifically, 9, 6, 9, and 5 SNPs were associated with the presence of osteoporosis, non-vertebral fractures, vertebral fractures, and any fracture, respectively. Collectively, 35 of the 95 SNPs (36.8%) were associated with one or more osteoporosis-related trait in Korean subjects. Of the 35 SNPs, 19 SNPs (54.3%) were also associated with one or more osteoporosis-related traits in East Asian populations. Twelve SNPs were associated with low BMD in the Chinese and Japanese cohorts. Specifically, 3, 4, and 2 SNPs were associated with the presence of hip fractures, vertebral fractures, and any fracture, respectively. Conclusions: Our results identified the common SNPs of osteoporosis-related traits in both Caucasian and East Asian populations. These SNPs should be further investigated to assess whether they are true genetic markers of osteoporosis.
Abstract
Background: Most reported genome-wide association studies (GWAS) seeking to identify the loci of osteoporosis-related traits have involved Caucasian populations. We aimed to identify the single nucleotide polymorphisms (SNPs) of osteoporosis-related traits among East Asian populations from the bone mineral density (BMD)-related loci of an earlier GWAS meta-analysis. Methods: A total of 95 SNPs, identified at the discovery stage of the largest GWAS meta-analysis of BMD, were tested to determine associations with osteoporosis-related traits (BMD, osteoporosis, or fracture) in Korean subjects (n=1,269). The identified SNPs of osteoporosis-related traits in Korean subjects were included in the replication analysis using Chinese (n=2,327) and Japanese (n=768) cohorts. Results: A total of 17 SNPs were associated with low BMD in Korean subjects. Specifically, 9, 6, 9, and 5 SNPs were associated with the presence of osteoporosis, non-vertebral fractures, vertebral fractures, and any fracture, respectively. Collectively, 35 of the 95 SNPs (36.8%) were associated with one or more osteoporosis-related trait in Korean subjects. Of the 35 SNPs, 19 SNPs (54.3%) were also associated with one or more osteoporosis-related traits in East Asian populations. Twelve SNPs were associated with low BMD in the Chinese and Japanese cohorts. Specifically, 3, 4, and 2 SNPs were associated with the presence of hip fractures, vertebral fractures, and any fracture, respectively. Conclusions: Our results identified the common SNPs of osteoporosis-related traits in both Caucasian and East Asian populations. These SNPs should be further investigated to assess whether they are true genetic markers of osteoporosis.
참고문헌 (22)
- NIH Consensus Development Panel on Osteoporosis, Prevention, Diagnosis and Therapy, "Osteoporosis prevention, diagnosis, and therapy", JAMA, 285, pp.785~795 (2001)
- Choi HJ, "Burden of osteoporosis in adults in Korea : a national health insurance database study", J Bone Miner Metab, 30, pp.54~58 (2012)
- Hong-Wen Deng, "Genome-wide Association Studies for Osteoporosis: A 2013 Update", 대한골대사학회지, 21(2), pp.98~114 (2014), 대한골대사학회
- Ralston SH, "Genetics of osteoporosis", Endocr Rev, 31, pp.629~662 (2010)
- Gullberg B, "World-wide projections for hip fracture", Osteoporos Int, 7, pp.407~413 (1997)
- 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)
- Fu J, "Multi-ethnic studies in complex traits", Hum Mol Genet, 20, pp.R206~R213 (2011)
- Gudbjartsson DF, "Variants conferring risk of atrial fibrillation on chromosome 4q25", Nature, 448, pp.353~357 (2007)
- Lee SH, "Prediction of future osteoporotic fracture occurrence by genetic profiling : A 6-year follow-up observational study", J Clin Endocrinol Metab, 101, pp.1215~1224 (2016)
- Nathan M, "Osteophyte formation in the vertebral column : a review of the etiologic factors--Part II", Contemp Orthop, 29, pp.113~119 (1994)
- Kanis JA, "The diagnosis of osteoporosis", J Bone Miner Res, 9, pp.1137~1141 (1994)
- Moon DH, "Cross-calibration of bone mineral density between two different dual X-ray absorptiometry systems : hologic QDR 4500-A and lunar EXPERT-XL", Korean J Nucl Med, 33, pp.282~288 (1999)
- Kiel D., "Assessing vertebral fractures. National Osteoporosis Foundation Working Group on vertebral fractures", J Bone Miner Res, 10, pp.518~523 (1995)
- Genant HK, "Vertebral fracture assessment using a semiquantitative technique", J Bone Miner Res, 8, pp.1137~1148 (1993)
- Yang TL, "Genetic variants in the SOX6 gene are associated with bone mineral density in both Caucasian and Chinese populations", Osteoporos Int, 23, pp.781~787 (2012)
- Guo Y, "Genome-wide association study identifies ALDH7A1 as a novel susceptibility gene for osteoporosis", PLoS Genet, 6, pp.e1000806~ (2010)
- Ikeda K, "Promoter analysis of mouse estrogen-responsive finger protein(efp)gene : mouse efp promoter contains an E-box that is also conserved in human", Gene, 216, pp.155~162 (1998)
- Braun A, "Technology challenges in screening single gene disorders", Eur J Pediatr, 162(Suppl 1), pp.S13~S16 (2003)
- Mein CA, "Evaluation of single nucleotide polymorphism typing with invader on PCR amplicons and its automation", Genome Res, 10, pp.330~343 (2000)
- Styrkarsdottir U, "European bone mineral density loci are also associated with BMD in East-Asian populations", PLoS One, 5, pp.e13217~ (2010)
- Kim YA, "Replication of Caucasian loci associated with bone mineral density in Koreans", Osteoporos Int, 24, pp.2603~2610 (2013)
- Cummings SR, "Epidemiology and outcomes of osteoporotic fractures", Lancet, 359, pp.1761~1767 (2002)