Identification of Known and Novel Long Noncoding RNAs Potentially Responsible for the Effects of Bone Mineral Density (BMD) Genomewide Association Study (GWAS) Loci.
Identification of Known and Novel Long Noncoding RNAs Potentially Responsible for the Effects of Bone Mineral Density (BMD) Genomewide Association Study (GWAS) Loci.
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DOI：
10.1002/jbmr.4622
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发表时间：
2022-08
影响因子：
6.2
通讯作者：
Farber, Charles R.
中科院分区：
文献类型：
--
作者：
Abood, Abdullah;Mesner, Larry;Rosenow, Will;Al-Barghouthi, Basel M.;Horowitz, Nina;Morgan, Elise F.;Gerstenfeld, Louis C.;Farber, Charles R.
骨质疏松症是一种最常见的影响骨骼的复杂疾病，以低骨密度为特征，是一个重大的社会健康问题。全基因组关联研究(GWASs)已经确定了1100多个影响BMD的关联。已有研究表明，对长非编码RNA(LncRNAs)的干扰会影响骨密度和骨细胞的活性；然而，lncRNAs参与骨密度的遗传调控的程度尚不清楚。在这里，我们结合了对人类髋臼骨碎片中等位基因失衡(AI)的分析，以及使用来自基因组-组织表达(GTEx)项目的数据进行的转录组范围关联研究(TWAS)和表达数量性状座位(EQTL)共定位分析，以确定可能与GWAS关联的lncRNAs。我们在骨骼中发现了27个LncRNAs，它们位于BMD Gwas关联的附近，并含有显示AI的单核苷酸多态(SNPs)。利用GTEx数据，我们另外鉴定了31个LncRNA的表达(错误发现率[Fdr]校正 <； 0.05)与TWA骨密度相关，并具有共定位eQTL(区域共定位概率[RCP] >； 0.1)。这58个LncRNA分布在43个BMD协会中。为了进一步支持已识别的lncRNAs的因果作用，我们发现58个lncRNAs中有23个作为成骨细胞分化的功能而差异表达。我们的方法确定了可能与骨密度和骨质疏松症相关的lncRNAs，并提示lncRNAs在骨质疏松的遗传学中发挥了作用。©2022作者。《骨与矿物研究杂志》由Wiley期刊有限责任公司代表美国骨与矿物研究学会(ASBMR)出版。
Osteoporosis, characterized by low bone mineral density (BMD), is the most common complex disease affecting bone and constitutes a major societal health problem. Genome‐wide association studies (GWASs) have identified over 1100 associations influencing BMD. It has been shown that perturbations to long noncoding RNAs (lncRNAs) influence BMD and the activities of bone cells; however, the extent to which lncRNAs are involved in the genetic regulation of BMD is unknown. Here, we combined the analysis of allelic imbalance (AI) in human acetabular bone fragments with a transcriptome‐wide association study (TWAS) and expression quantitative trait loci (eQTL) colocalization analysis using data from the Genotype‐Tissue Expression (GTEx) project to identify lncRNAs potentially responsible for GWAS associations. We identified 27 lncRNAs in bone that are located in proximity to a BMD GWAS association and harbor single‐nucleotide polymorphisms (SNPs) demonstrating AI. Using GTEx data we identified an additional 31 lncRNAs whose expression was associated (false discovery rate [FDR] correction < 0.05) with BMD through TWAS and had a colocalizing eQTL (regional colocalization probability [RCP] > 0.1). The 58 lncRNAs are located in 43 BMD associations. To further support a causal role for the identified lncRNAs, we show that 23 of the 58 lncRNAs are differentially expressed as a function of osteoblast differentiation. Our approach identifies lncRNAs that are potentially responsible for BMD GWAS associations and suggest that lncRNAs play a role in the genetics of osteoporosis. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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影响因子：
56.9
作者：
Cheng, J;Kapranov, P;Gingeras, TR
通讯作者：
Gingeras, TR
影响因子：
12.3
作者：
Marchese FP;Raimondi I;Huarte M
通讯作者：
Huarte M
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
6.2
作者：
Burge, Russel;Dawson-Hughes, Bess;Tosteson, Anna
通讯作者：
Tosteson, Anna
影响因子：
3.7
作者：
Farr JN;Roforth MM;Fujita K;Nicks KM;Cunningham JM;Atkinson EJ;Therneau TM;McCready LK;Peterson JM;Drake MT;Monroe DG;Khosla S
通讯作者：
Khosla S