Twelve New Genomic Loci Associated With Bone Mineral Density
Aiming to identify more genomic loci associated with bone mineral density (BMD), we conducted a joint association analysis of 2 genome-wide association study (GWAS) by the integrative association method multi-trait analysis of GWAS (MTAG). The first one is the single GWAS of estimated heel BMD (eBMD...
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2020.00243/full |
| _version_ | 1818159427573776384 |
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| author | Lu Liu Lu Liu Lu Liu Min Zhao Min Zhao Zong-Gang Xie Ju Liu Hui-Ping Peng Yu-Fang Pei Hong-Peng Sun Hong-Peng Sun Lei Zhang Lei Zhang |
| author_facet | Lu Liu Lu Liu Lu Liu Min Zhao Min Zhao Zong-Gang Xie Ju Liu Hui-Ping Peng Yu-Fang Pei Hong-Peng Sun Hong-Peng Sun Lei Zhang Lei Zhang |
| author_sort | Lu Liu |
| collection | DOAJ |
| description | Aiming to identify more genomic loci associated with bone mineral density (BMD), we conducted a joint association analysis of 2 genome-wide association study (GWAS) by the integrative association method multi-trait analysis of GWAS (MTAG). The first one is the single GWAS of estimated heel BMD (eBMD) in the UK biobank (UKB) cohort (N = 426,824), and the second one is the GWAS meta-analysis of total body BMD (TB-BMD) in 66,628 participants from 30 studies. Approximate conditional association analysis was performed in the identified novel loci to identify secondary association signal. Statistical fine-mapping was conducted to prioritize plausible credible risk variants (CRVs). Candidate genes were prioritized based on the analyses of cis- expression quantitative trait locus (cis-eQTL) and cis-protein QTL (cis-pQTL) information as well as the functional category of the SNP. By integrating the information carried in over 490,000 participants, this largest joint analysis of BMD GWAS identified 12 novel genomic loci at the genome-wide significance level (GWS, p = 5.0 × 10−8), nine of which were for eBMD and four were for TB-BMD, explaining an additional 0.11 and 0.23% heritability for the two traits, respectively. These loci include 1p33 (lead SNP rs10493130, peBMD = 3.19 × 10−8), 5q13.2 (rs4703589, peBMD = 4.78 × 10−8), 5q31.3 (rs9324887, pTB−BMD = 1.36 × 10−9), 6p21.32 (rs6905837, peBMD = 3.32 × 10−8), 6q14.1 (rs10806234, peBMD = 2.63 × 10−8), 7q21.11 (rs10806234, pTB−BMD = 3.37 × 10−8), 8q24.12 (rs11995866, peBMD = 6.72 × 10−9), 12p13.31 (rs1639122, peBMD = 4.43 × 10−8), 12p12.1 (rs58489179, peBMD = 4.74 × 10−8), 12q24.23 (rs75499226, peBMD = 1.44 × 10−8), 19q13.31 (rs7255083, pTB−BMD = 2.18 × 10−8) and 22q11.23 (rs13056137, pTB−BMD = 2.54 × 10−8). All lead SNPs in these 12 loci are nominally significant in both original studies as well as consistent in effect direction between them, providing solid evidence of replication. Approximate conditional analysis identified one secondary signal in 5q13.2 (rs11738874, pconditional = 5.06 × 10−9). Statistical fine-mapping analysis prioritized 269 CRVs. A total of 65 candidate genes were prioritized, including those with known biological function to bone development (such as FGF1, COL11A2 and DEPTOR). Our findings provide novel insights into a better understanding of the genetic mechanism underlying bone development as well as candidate genes for future functional investigation. |
| first_indexed | 2024-12-11T15:45:49Z |
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| spelling | doaj.art-b64a6b483b744b5fa3d30d753558bc8c2022-12-22T00:59:42ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922020-04-011110.3389/fendo.2020.00243527099Twelve New Genomic Loci Associated With Bone Mineral DensityLu Liu0Lu Liu1Lu Liu2Min Zhao3Min Zhao4Zong-Gang Xie5Ju Liu6Hui-Ping Peng7Yu-Fang Pei8Hong-Peng Sun9Hong-Peng Sun10Lei Zhang11Lei Zhang12Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Jiangsu, ChinaJiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Jiangsu, ChinaKunshan Hospital of Traditional Chinese Medicine, Jiangsu, ChinaCenter for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Jiangsu, ChinaJiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Jiangsu, ChinaThe Second Affiliated Hospital of Soochow University, Jiangsu, ChinaKunshan Hospital of Traditional Chinese Medicine, Jiangsu, ChinaKunshan Hospital of Traditional Chinese Medicine, Jiangsu, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Medical College of Soochow University, Jiangsu, ChinaJiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Jiangsu, ChinaDepartment of Children Health and Social Medicine, School of Public Health, Medical College of Soochow University, Jiangsu, ChinaCenter for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Jiangsu, ChinaJiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Jiangsu, ChinaAiming to identify more genomic loci associated with bone mineral density (BMD), we conducted a joint association analysis of 2 genome-wide association study (GWAS) by the integrative association method multi-trait analysis of GWAS (MTAG). The first one is the single GWAS of estimated heel BMD (eBMD) in the UK biobank (UKB) cohort (N = 426,824), and the second one is the GWAS meta-analysis of total body BMD (TB-BMD) in 66,628 participants from 30 studies. Approximate conditional association analysis was performed in the identified novel loci to identify secondary association signal. Statistical fine-mapping was conducted to prioritize plausible credible risk variants (CRVs). Candidate genes were prioritized based on the analyses of cis- expression quantitative trait locus (cis-eQTL) and cis-protein QTL (cis-pQTL) information as well as the functional category of the SNP. By integrating the information carried in over 490,000 participants, this largest joint analysis of BMD GWAS identified 12 novel genomic loci at the genome-wide significance level (GWS, p = 5.0 × 10−8), nine of which were for eBMD and four were for TB-BMD, explaining an additional 0.11 and 0.23% heritability for the two traits, respectively. These loci include 1p33 (lead SNP rs10493130, peBMD = 3.19 × 10−8), 5q13.2 (rs4703589, peBMD = 4.78 × 10−8), 5q31.3 (rs9324887, pTB−BMD = 1.36 × 10−9), 6p21.32 (rs6905837, peBMD = 3.32 × 10−8), 6q14.1 (rs10806234, peBMD = 2.63 × 10−8), 7q21.11 (rs10806234, pTB−BMD = 3.37 × 10−8), 8q24.12 (rs11995866, peBMD = 6.72 × 10−9), 12p13.31 (rs1639122, peBMD = 4.43 × 10−8), 12p12.1 (rs58489179, peBMD = 4.74 × 10−8), 12q24.23 (rs75499226, peBMD = 1.44 × 10−8), 19q13.31 (rs7255083, pTB−BMD = 2.18 × 10−8) and 22q11.23 (rs13056137, pTB−BMD = 2.54 × 10−8). All lead SNPs in these 12 loci are nominally significant in both original studies as well as consistent in effect direction between them, providing solid evidence of replication. Approximate conditional analysis identified one secondary signal in 5q13.2 (rs11738874, pconditional = 5.06 × 10−9). Statistical fine-mapping analysis prioritized 269 CRVs. A total of 65 candidate genes were prioritized, including those with known biological function to bone development (such as FGF1, COL11A2 and DEPTOR). Our findings provide novel insights into a better understanding of the genetic mechanism underlying bone development as well as candidate genes for future functional investigation.https://www.frontiersin.org/article/10.3389/fendo.2020.00243/fullbone mineral densitygenome-wide association studyosteoporosisjoint analysisMTAG |
| spellingShingle | Lu Liu Lu Liu Lu Liu Min Zhao Min Zhao Zong-Gang Xie Ju Liu Hui-Ping Peng Yu-Fang Pei Hong-Peng Sun Hong-Peng Sun Lei Zhang Lei Zhang Twelve New Genomic Loci Associated With Bone Mineral Density Frontiers in Endocrinology bone mineral density genome-wide association study osteoporosis joint analysis MTAG |
| title | Twelve New Genomic Loci Associated With Bone Mineral Density |
| title_full | Twelve New Genomic Loci Associated With Bone Mineral Density |
| title_fullStr | Twelve New Genomic Loci Associated With Bone Mineral Density |
| title_full_unstemmed | Twelve New Genomic Loci Associated With Bone Mineral Density |
| title_short | Twelve New Genomic Loci Associated With Bone Mineral Density |
| title_sort | twelve new genomic loci associated with bone mineral density |
| topic | bone mineral density genome-wide association study osteoporosis joint analysis MTAG |
| url | https://www.frontiersin.org/article/10.3389/fendo.2020.00243/full |
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