A Multi-Marker Test for Analyzing Paired Genetic Data in Transplantation.
A Multi-Marker Test for Analyzing Paired Genetic Data in Transplantation.
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DOI：
10.3389/fgene.2021.745773
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发表时间：
2021
影响因子：
3.7
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Arthur VL;Li Z;Cao R;Oetting WS;Israni AK;Jacobson PA;Ritchie MD;Guan W;Chen J
新出现的证据表明，基因组非HLA（人类白细胞抗原）区域的供体/受体匹配可能会影响移植结果，认识到这些匹配效应可能会增加移植遗传学研究的力量。大多数可用的匹配分数仅考虑单核苷酸多态性（SNP）匹配或将多个基因编码区的SNP匹配分数相加，这使得解释关联结果具有挑战性。我们提出了一种多标记联合评分测试（JST），以联合测试受体基因型SNP效应和基于基因的匹配评分与移植结果之间的关联。该方法利用本征分解作为降维技术，通过降低测试的自由度来潜在地增加统计功效。此外，JST允许匹配效应和受体基因型效应遵循不同的生物学机制，这是其他多标记方法所不具备的。大量的模拟研究表明，JST是有竞争力的，与现有的方法相比，如序列核关联测试（SKAT），特别是在场景中，相关的SNP是在低连锁不平衡与非相关的SNP或在基因区域包含大量的SNP。将该方法应用于来自肾移植研究的配对供体/受体遗传数据，产生了可能与移植后急性排斥反应发生率相关的各种基因区域。
Emerging evidence suggests that donor/recipient matching in non-HLA (human leukocyte antigen) regions of the genome may impact transplant outcomes and recognizing these matching effects may increase the power of transplant genetics studies. Most available matching scores account for either single-nucleotide polymorphism (SNP) matching only or sum these SNP matching scores across multiple gene-coding regions, which makes it challenging to interpret the association findings. We propose a multi-marker Joint Score Test (JST) to jointly test for association between recipient genotype SNP effects and a gene-based matching score with transplant outcomes. This method utilizes Eigen decomposition as a dimension reduction technique to potentially increase statistical power by decreasing the degrees of freedom for the test. In addition, JST allows for the matching effect and the recipient genotype effect to follow different biological mechanisms, which is not the case for other multi-marker methods. Extensive simulation studies show that JST is competitive when compared with existing methods, such as the sequence kernel association test (SKAT), especially under scenarios where associated SNPs are in low linkage disequilibrium with non-associated SNPs or in gene regions containing a large number of SNPs. Applying the method to paired donor/recipient genetic data from kidney transplant studies yields various gene regions that are potentially associated with incidence of acute rejection after transplant.
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影响因子：
2.1
作者：
Fan, Ruzong;Wang, Yifan;Mills, James L.;Wilson, Alexander F.;Bailey-Wilson, Joan E.;Xiong, Momiao
通讯作者：
Xiong, Momiao
影响因子：
4.6
作者：
Iribarren C;Lu M;Jorgenson E;Martínez M;Lluis-Ganella C;Subirana I;Salas E;Elosua R
通讯作者：
Elosua R
影响因子：
12.3
作者：
Li YR;van Setten J;Verma SS;Lu Y;Holmes MV;Gao H;Lek M;Nair N;Chandrupatla H;Chang B;Karczewski KJ;Wong C;Mohebnasab M;Mukhtar E;Phillips R;Tragante V;Hou C;Steel L;Lee T;Garifallou J;Guettouche T;Cao H;Guan W;Himes A;van Houten J;Pasquier A;Yu R;Carrigan E;Miller MB;Schladt D;Akdere A;Gonzalez A;Llyod KM;McGinn D;Gangasani A;Michaud Z;Colasacco A;Snyder J;Thomas K;Wang T;Wu B;Alzahrani AJ;Al-Ali AK;Al-Muhanna FA;Al-Rubaish AM;Al-Mueilo S;Monos DS;Murphy B;Olthoff KM;Wijmenga C;Webster T;Kamoun M;Balasubramanian S;Lanktree MB;Oetting WS;Garcia-Pavia P;MacArthur DG;de Bakker PI;Hakonarson H;Birdwell KA;Jacobson PA;Ritchie MD;Asselbergs FW;Israni AK;Shaked A;Keating BJ
通讯作者：
Keating BJ
影响因子：
2.1
作者：
Gauderman, W. James;Murcray, Cassandra;Conti, David V.
通讯作者：
Conti, David V.
影响因子：
9.8
作者：
Chen, Han;Huffman, Jennifer E.;Lin, Xihong
通讯作者：
Lin, Xihong