A systematic heritability analysis of the human whole blood transcriptome.

A systematic heritability analysis of the human whole blood transcriptome.
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DOI:
10.1007/s00439-014-1524-3
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发表时间:
2015-03
期刊:
影响因子:
5.3
通讯作者:
Levy, Daniel
Levy, Daniel
中科院分区:
生物学2区
文献类型:
--
作者:
Huan, Tianxiao;Liu, Chunyu;Joehanes, Roby;Zhang, Xiaoling;Chen, Brian H.;Johnson, Andrew D.;Yao, Chen;Courchesne, Paul;O'Donnell, Christopher J.;Munson, Peter J.;Levy, Daniel

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全基因组表达数量性状位点(eQTL)定位可以揭示调节基因表达的常见遗传变异。除了绘制eqtl图谱外,我们还系统地评估了Framingham心脏研究中5626名参与者的全血转录组的遗传性。在所有基因表达测量中,约40%显示出可遗传的证据(,(p<0.05)),平均遗传率估计为0.13,10%显示。为了确定eqtl在促进表型差异和疾病易感性中的作用,我们研究了不同遗传力类别中顺式/反式eqtl的比例,发现遗传力高的基因更有可能具有解释相应基因表达大比例方差的顺式eqtl。单个顺式eqtl平均解释0.33-0.53个转录本的方差,而单个反式eqtl仅解释0.02-0.07个转录本的方差。顶端的顺式对等qtl在相应的基因中,当其较大时,往往解释更多的变异。以体重指数(BMI)为例,我们将GWAS snp和BMI差异表达基因的顺式/反式qtl交联。我们发现16p11.2中的BMI GWAS snp(例如rs7359397)与几个BMI差异表达基因(例如SULT1A1, SPNS1和TUFM)以顺式方式相关。这些BMI特征基因比GWAS snp更能解释BMI变异的比例。我们的研究结果揭示了eqtl对人类全血转录组遗传力的影响及其与表型差异的关系。
Genome-wide expression quantitative trait locus (eQTL) mapping may reveal common genetic variants regulating gene expression. In addition to mapping eQTLs, we systematically evaluated the heritability of the whole blood transcriptome in 5626 participants from the Framingham Heart Study. Of all gene expression measurements, about 40% exhibit evidence of being heritable (, (p<0.05]), the average heritability was estimated to be 0.13, and 10% display . In order to identify the role of eQTLs in promoting phenotype differences and disease susceptibility, we investigated the proportion of cis/trans eQTLs in different heritability categories and discovered that genes with higher heritability are more likely to have cis eQTLs that explain large proportions of variance in the expression of the corresponding genes. Single cis eQTLs explain 0.33–0.53 of variance in transcripts on average, whereas single trans eQTLs only explain 0.02–0.07. The top cis eQTLs tend to explain more variance in the corresponding gene when its is greater. Taking body mass index (BMI) as a case study, we cross-linked cis/trans eQTLs with both GWAS SNPs and differentially expressed genes for BMI. We discovered that BMI GWAS SNPs in 16p11.2 (e.g., rs7359397) are associated with several BMI differentially expressed genes in a cis manner (e.g. SULT1A1, SPNS1, and TUFM). These BMI signature genes explain a much larger proportion of variance in BMI than do the GWAS SNPs. Our results shed light the impact of eQTLs on the heritability of the human whole blood transcriptome and its relations to phenotype differences.
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影响因子: 30.8
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来自1,092个人基因组的遗传变异的综合图。
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