Enhanced Identification of Novel Potential Variants for Appendicular Lean Mass by Leveraging Pleiotropy With Bone Mineral Density.
Enhanced Identification of Novel Potential Variants for Appendicular Lean Mass by Leveraging Pleiotropy With Bone Mineral Density.
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利用骨矿物质密度的多效性增强对阑尾瘦肉块新的潜在变异的识别
DOI：
10.3389/fimmu.2021.643894
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发表时间：
2021
影响因子：
7.3
通讯作者：
Lou HL
中科院分区：
文献类型：
--
作者：
Peng C;Liu F;Su KJ;Lin X;Song YQ;Shen J;Hu SD;Chen QC;Yuan HH;Li WX;Zeng CP;Deng HW;Lou HL
已发现非典型性瘦体重（ALM）和骨矿物质密度（BMD）之间存在密切关系。这可能是由于一个共同的遗传基础，称为多效性。通过利用BMD的多效性，本研究的目的是检测更多潜在的ALM遗传变异。使用条件错误发现率（cFDR）方法，对ALM（n = 73，420）和BMD（n = 10，414）的两项大型独立全基因组关联研究（GWAS）的汇总统计量进行了联合分析。发现了ALM和BMD的强多效性富集和26个新的潜在多效性SNP。我们鉴定了156个ALM的SNP（cFDR <0.05），其中74个是先前GWAS的重复，82个是与ALM潜在相关的新SNP。在基因表达测定中部分验证了由31个新SNP（13个多效性和18个ALM特异性）注释的11个基因。功能富集分析表明，对应于新的潜在SNPs的基因富集在GO术语和/或KEGG途径中，这些途径在肌肉发育和/或BMD代谢中起重要作用（adjP <0.05）。在蛋白质间相互作用分析中，发现相应基因所产生的蛋白质之间存在丰富的相互作用。总之，本研究与我们最近进行的其他研究一样，证明了cFDR方法用于增强性状相关遗传变异检测的上级效率和可靠性。我们的研究结果揭示了新的见解，除了共享的遗传基础的ALM和BMD的遗传变异性的ALM。
Strong relationships have been found between appendicular lean mass (ALM) and bone mineral density (BMD). It may be due to a shared genetic basis, termed pleiotropy. By leveraging the pleiotropy with BMD, the aim of this study was to detect more potential genetic variants for ALM. Using the conditional false discovery rate (cFDR) methodology, a combined analysis of the summary statistics of two large independent genome wide association studies (GWAS) of ALM (n = 73,420) and BMD (n = 10,414) was conducted. Strong pleiotropic enrichment and 26 novel potential pleiotropic SNPs were found for ALM and BMD. We identified 156 SNPs for ALM (cFDR <0.05), of which 74 were replicates of previous GWASs and 82 were novel SNPs potentially-associated with ALM. Eleven genes annotated by 31 novel SNPs (13 pleiotropic and 18 ALM specific) were partially validated in a gene expression assay. Functional enrichment analysis indicated that genes corresponding to the novel potential SNPs were enriched in GO terms and/or KEGG pathways that played important roles in muscle development and/or BMD metabolism (adjP <0.05). In protein–protein interaction analysis, rich interactions were demonstrated among the proteins produced by the corresponding genes. In conclusion, the present study, as in other recent studies we have conducted, demonstrated superior efficiency and reliability of the cFDR methodology for enhanced detection of trait-associated genetic variants. Our findings shed novel insight into the genetic variability of ALM in addition to the shared genetic basis underlying ALM and BMD.
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影响因子：
4.6
作者：
Kawane T;Qin X;Jiang Q;Miyazaki T;Komori H;Yoshida CA;Matsuura-Kawata VKDS;Sakane C;Matsuo Y;Nagai K;Maeno T;Date Y;Nishimura R;Komori T
通讯作者：
Komori T
影响因子：
4.5
作者：
Paternoster L;Lorentzon M;Lehtimäki T;Eriksson J;Kähönen M;Raitakari O;Laaksonen M;Sievänen H;Viikari J;Lyytikäinen LP;Mellström D;Karlsson M;Ljunggren O;Grundberg E;Kemp JP;Sayers A;Nethander M;Evans DM;Vandenput L;Tobias JH;Ohlsson C
通讯作者：
Ohlsson C
影响因子：
30.8
作者：
Rivadeneira, Fernando;Styrkarsdottir, Unnur;Estrada, Karol;Halldorsson, Bjarni V.;Hsu, Yi-Hsiang;Richards, J. Brent;Zillikens, M. Carola;Kavvoura, Fotini K.;Amin, Najaf;Aulchenko, Yurii S.;Cupples, L. Adrienne;Deloukas, Panagiotis;Demissie, Serkalem;Grundberg, Elin;Hofman, Albert;Kong, Augustine;Karasik, David;van Meurs, Joyce B.;Oostra, Ben;Pastinen, Tomi;Pols, Huibert A. P.;Sigurdsson, Gunnar;Soranzo, Nicole;Thorleifsson, Gudmar;Thorsteinsdottir, Unnur;Williams, Frances M. K.;Wilson, Scott G.;Zhou, Yanhua;Ralston, Stuart H.;van Duijn, Cornelia M.;Spector, Timothy;Kiel, Douglas P.;Stefansson, Kari;Ioannidis, John P. A.;Uitterlinden, Andre G.
通讯作者：
Uitterlinden, Andre G.
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
影响因子：
6.2
作者：
Arden, NK;Spector, TD
通讯作者：
Spector, TD