Sharing information between related diseases using Bayesian joint fine mapping increases accuracy and identifies novel associations in six immune mediated diseases
Sharing information between related diseases using Bayesian joint fine mapping increases accuracy and identifies novel associations in six immune mediated diseases
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使用贝叶斯联合精细映射在相关疾病之间共享信息可提高准确性并识别六种免疫介导疾病的新关联
DOI：
10.1101/553560
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Asimit J
中科院分区：
文献类型：
--
作者：
Asimit J
成千上万的遗传变异与人类疾病风险相关，但连锁不平衡（LD）阻碍了因果变异的精细定位。我们发现，逐步回归，并在较小程度上，随机搜索精细映射可以错误识别为因果，SNP联合标记不同的因果变异。免疫介导的疾病（IMD）之间频繁共享的因果变异促使我们开发了一种计算效率高的多项式精细映射（MFM）方法，该方法在贝叶斯框架中借用疾病之间的信息。我们表明，MFM具有更高的准确性比单一疾病分析时，共享的因果变异存在，否则可以忽略不计的精度损失。将MFM应用于来自六个IMD的数据，揭示了在个体疾病分析中未检测到的因果变异，包括在IL2RA中，我们使用来自基因型选择个体的分选的CD4+T细胞中的等位基因特异性表达来确认多个因果变异的功能效应。MFM有可能提高相关疾病的精细定位分辨率，从而能够识别相关的细胞和分子表型。
Thousands of genetic variants have been associated with human disease risk, but linkage disequilibrium (LD) hinders fine-mapping the causal variants. We show that stepwise regression, and, to a lesser extent, stochastic search fine mapping can mis-identify as causal, SNPs which jointly tag distinct causal variants. Frequent sharing of causal variants between immune-mediated diseases (IMD) motivated us to develop a computationally efficient multinomial fine-mapping (MFM) approach that borrows information between diseases in a Bayesian framework. We show that MFM has greater accuracy than single disease analysis when shared causal variants exist, and negligible loss of precision otherwise. Applying MFM to data from six IMD revealed causal variants undetected in individual disease analysis, including inIL2RAwhere we confirm functional effects of multiple causal variants using allele-specific expression in sorted CD4+T cells from genotype-selected individuals. MFM has the potential to increase fine-mapping resolution in related diseases enabling the identification of associated cellular and molecular phenotypes.
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影响因子：
4.5
作者：
C. Wallace;A. Cutler;Nikolas Pontikos;M. Pekalski;O. Burren;J. Cooper;Arcadio Rubio García;R. Ferreira;Hui Guo;N. Walker;D. Smyth;S. Rich;S. Onengut-Gumuscu;S. Sawcer;M. Ban;S. Richardson;J. Todd;L. Wicker
通讯作者：
C. Wallace;A. Cutler;Nikolas Pontikos;M. Pekalski;O. Burren;J. Cooper;Arcadio Rubio García;R. Ferreira;Hui Guo;N. Walker;D. Smyth;S. Rich;S. Onengut-Gumuscu;S. Sawcer;M. Ban;S. Richardson;J. Todd;L. Wicker
多发性硬化症基因组图谱：外周免疫细胞和常驻小胶质细胞在易感性中的作用
DOI：
--
发表时间：
2017
期刊：
bioRxiv
影响因子：
--
作者：
N. Patsopoulos;S. Baranzini;A. Santaniello;P. Shoostari;C. Cotsapas;G. Wong;A. Beecham;T. James;J. Replogle;I. Vlachos;C. McCabe;T. Pers;A. Brandes;C. White;B. Keenan;M. Cimpean;P. Winn;I. Panteliadis;A. Robbins;T. Andlauer;O. Zarzycki;B. Dubois;A. Goris;H. Søndergaard;F. Sellebjerg;P. Sørensen;H. Ullum;L. W. Thoerner;J. Saarela;I. Rebeix;V. Damotte;B. Fontaine;L. Noel;M. Lathrop;S. Vukusik;A. Berthele;V. Biberacher;D. Buck;C. Gasperi;C. Graetz;V. Grummel;B. Hemmer;M. Hoshi;B. Knier;T. Korn;C. Lill;F. Luessi;M. Mühlau;F. Zipp;E. Dardiotis;C. Agliardi;A. Amoroso;N. Barizzone;M. Benedetti;L. Bernardinelli;P. Cavalla;F. Clarelli;G. Comi;D. Cusi;F. Esposito;L. Ferré;D. Galimberti;C. Guaschino;M. Leone;V. Martinelli;L. Moiola;M. Salvetti;M. Sorosina;D. Vecchio;A. Zauli;S. Santoro;M. Zuccalà;J. Mescheriakova;C. Duijn;S. Bos;E. Celius;A. Spurkland;M. Comabella;X. Montalban;L. Alfredsson;I. Bomfim;D. Gómez;J. Hillert;M. Jagodic;M. Lindén;F. Piehl;I. Jelcic;R. Martin;M. Sospedra;A. Baker;M. Ban;C. Hawkins;P. Hysi;S. Kalra;F. Karpe;J. Khadake;G. Lachance;P. Molyneux;M. Neville;J. Thorpe;E. Bradshaw;S. Caillier;P. Calabresi;B. Cree;A. Cross;M. Davis;P. D. Bakker;S. Delgado;M. Dembele;K. Edwards;K. Fitzgerald;I. Frohlich;P. Gourraud;J. Haines;H. Hakonarson;D. Kimbrough;N. Isobe;I. Konidari;E. Lathi;MH Lee;T. Li;D. An;A. Zimmer;A. Lo;L. Madireddy;C. Manrique;M. Mitrovič;M. Olah;E. Patrick;M. Pericak;L. Piccio;C. Schaefer;H. Weiner;K. Lage;A. Compston;D. Hafler;H. Harbo;S. Hauser;G. Stewart;S. D'alfonso;G. Hadjigeorgiou;B. Taylor;L. Barcellos;D. Booth;R. Hintzen;I. Kockum;F. Martinelli;J. McCauley;J. Oksenberg;A. Oturai;S. Sawcer;A. Ivinson;T. Olsson;P. D. Jager;M. Barclay;L. Peyrin;M. Chamaillard;J. Colombe;M. Cottone;A. Croft;R. D'Incà;J. Halfvarson;K. Hanigan;P. Henderson;J. Hugot;A. Karban;N. Kennedy;M. Khan;M. Lémann;A. Levine;D. Massey;M. Milla;G. Montgomery;Sok Meng Evelyn Ng;I. Oikonomou;H. Peeters;D. Proctor;J. Rahier;R. Roberts;P. Rutgeerts;F. Seibold;L. Stronati;K. Taylor;L. Törkvist;Kullak Ublick;J. V. Limbergen;A. Gossum;M. Vatn;Hu Zhang;Wei Zhang
通讯作者：
Wei Zhang
用于下一代全基因组关联研究的灵活而准确的基因型插补方法。
影响因子：
4.5
作者：
Howie, Bryan N.;Donnelly, Peter;Marchini, Jonathan
通讯作者：
Marchini, Jonathan
Wnt酰化：眼见为实。
影响因子：
14.8
作者：
L. Berthiaume
通讯作者：
L. Berthiaume
活化T细胞中的染色体接触识别自身免疫性疾病候选基因
DOI：
10.1101/100958
发表时间：
2017
期刊：
--
影响因子：
--
作者：
Burren O
通讯作者：
Burren O