Dataset Information

European bone mineral density loci are also associated with BMD in East-Asian populations.

ABSTRACT: Most genome-wide association (GWA) studies have focused on populations of European ancestry with limited assessment of the influence of the sequence variants on populations of other ethnicities. To determine whether markers that we have recently shown to associate with Bone Mineral Density (BMD) in Europeans also associate with BMD in East-Asians we analysed 50 markers from 23 genomic loci in samples from Korea (n?=?1,397) and two Chinese Hong Kong sample sets (n?=?3,869 and n?=?785). Through this effort we identified fourteen loci that associated with BMD in East-Asian samples using a false discovery rate (FDR) of 0.05; 1p36 (ZBTB40, P?=?4.3×10(-9)), 1p31 (GPR177, P?=?0.00012), 3p22 (CTNNB1, P?=?0.00013), 4q22 (MEPE, P?=?0.0026), 5q14 (MEF2C, P?=?1.3×10(-5)), 6q25 (ESR1, P?=?0.0011), 7p14 (STARD3NL, P?=?0.00025), 7q21 (FLJ42280, P?=?0.00017), 8q24 (TNFRSF11B, P?=?3.4×10(-5)), 11p15 (SOX6, P?=?0.00033), 11q13 (LRP5, P?=?0.0033), 13q14 (TNFSF11, P?=?7.5×10(-5)), 16q24 (FOXL1, P?=?0.0010) and 17q21 (SOST, P?=?0.015). Our study marks an early effort towards the challenge of cataloguing bone density variants shared by many ethnicities by testing BMD variants that have been established in Europeans, in East-Asians.

SUBMITTER: Styrkarsdottir U

PROVIDER: S-EPMC2951352 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

European bone mineral density loci are also associated with BMD in East-Asian populations.

Styrkarsdottir Unnur U Halldorsson Bjarni V BV Gudbjartsson Daniel F DF Tang Nelson L S NL Koh Jung-Min JM Xiao Su-mei SM Kwok Timothy C Y TC Kim Ghi Su GS Chan Juliana C N JC Cherny Stacey S Lee Seung Hun SH Kwok Anthony A Ho Suzanne S Gretarsdottir Solveig S Kostic Jelena Pop JP Palsson Stefan Th ST Sigurdsson Gunnar G Sham Pak C PC Kim Beom-Jun BJ Kung Annie W C AW Kim Shin-Yoon SY Woo Jean J Leung Ping-C PC Kong Augustine A Thorsteinsdottir Unnur U Stefansson Kari K

PloS one 20101007 10

Most genome-wide association (GWA) studies have focused on populations of European ancestry with limited assessment of the influence of the sequence variants on populations of other ethnicities. To determine whether markers that we have recently shown to associate with Bone Mineral Density (BMD) in Europeans also associate with BMD in East-Asians we analysed 50 markers from 23 genomic loci in samples from Korea (n = 1,397) and two Chinese Hong Kong sample sets (n = 3,869 and n = 785). Through th ...[more]

PMID: 20949110

Similar Datasets

Project 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.

Project description:Genetic studies of bone mineral density (BMD) largely have been conducted in European populations. We therefore conducted a meta-analysis of six independent African ancestry cohorts to determine whether previously reported BMD loci identified in European populations were transferable to African ancestry populations. We included nearly 5000 individuals with both genetic data and assessments of BMD. Genotype imputation was conducted using the 1000G reference panel. We assessed single-nucleotide polymorphism (SNP) associations with femoral neck and lumbar spine BMD in each cohort separately, then combined results in fixed effects (or random effects if study heterogeneity was high, I2 index >60) inverse variance weighted meta-analyses. In secondary analyses, we conducted locus-based analyses of rare variants using SKAT-O. Mean age ranged from 12 to 68 years. One cohort included only men and another cohort included only women; the proportion of women in the other four cohorts ranged from 52% to 63%. Of 56 BMD loci tested, one locus, 6q25 (C6orf97, p = 8.87 × 10-4 ), was associated with lumbar spine BMD and two loci, 7q21 (SLC25A13, p = 2.84 × 10-4 ) and 7q31 (WNT16, p = 2.96 × 10-5 ), were associated with femoral neck BMD. Effects were in the same direction as previously reported in European ancestry studies and met a Bonferroni-adjusted p value threshold, the criteria for transferability to African ancestry populations. We also found associations that met locus-specific Bonferroni-adjusted p value thresholds in 11q13 (LRP5, p < 2.23 × 10-4 ), 11q14 (DCDC5, p < 5.35 × 10-5 ), and 17p13 (SMG6, p < 6.78 × 10-5 ) that were not tagged by European ancestry index SNPs. Rare single-nucleotide variants in AKAP11 (p = 2.32 × 10-2 ), MBL2 (p = 4.09 × 10-2 ), MEPE (p = 3.15 × 10-2 ), SLC25A13 (p = 3.03 × 10-2 ), STARD3NL (p = 3.35 × 10-2 ), and TNFRSF11A (p = 3.18 × 10-3 ) were also associated with BMD. The majority of known BMD loci were not transferable. Larger genetic studies of BMD in African ancestry populations will be needed to overcome limitations in statistical power and to identify both other loci that are transferable across populations and novel population-specific variants. © 2020 American Society for Bone and Mineral Research (ASBMR).

Dataset Information

European bone mineral density loci are also associated with BMD in East-Asian populations.

Publications

European bone mineral density loci are also associated with BMD in East-Asian populations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets