Tissue-specific impacts of aging and genetics on gene expression patterns in humans.
Tissue-specific impacts of aging and genetics on gene expression patterns in humans.
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DOI：
10.1038/s41467-022-33509-0
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发表时间：
2022-10-03
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
年龄是许多人类常见疾病的主要危险因素。在这里，我们量化了 948 名人类 27 个组织中遗传和衰老对基因表达模式的相对贡献。我们表明，在许多组织中，表达数量性状基因座的预测能力受到年龄的影响。联合模拟年龄和遗传学对转录水平变异的影响，我们发现组织之间的表达遗传力 (h2) 是一致的，而衰老的影响在 5 个组织中变化超过 20 倍。我们发现，虽然纯化选择的力量对生命早期表达的基因比生命晚期表达的基因更强（梅达沃的假设），但一些高度增殖的组织表现出相反的模式。这些非 Medawarian 组织表现出高癌症发生率和与表达年龄相关的体细胞突变。相比之下，基因控制下的基因则受到宽松的约束。我们共同证明了衰老和遗传学对表达表型的独特作用。年龄是许多疾病的危险因素，但衰老对分子表型的影响尚不完全清楚。在这里，作者量化了遗传学和衰老对人类 27 个组织的基因表达模式的相对贡献，表明年龄和遗传学在塑造表达表型方面各自发挥着不同的作用。
Age is the primary risk factor for many common human diseases. Here, we quantify the relative contributions of genetics and aging to gene expression patterns across 27 tissues from 948 humans. We show that the predictive power of expression quantitative trait loci is impacted by age in many tissues. Jointly modelling the contributions of age and genetics to transcript level variation we find expression heritability (h2) is consistent among tissues while the contribution of aging varies by >20-fold with in 5 tissues. We find that while the force of purifying selection is stronger on genes expressed early versus late in life (Medawar’s hypothesis), several highly proliferative tissues exhibit the opposite pattern. These non-Medawarian tissues exhibit high rates of cancer and age-of-expression-associated somatic mutations. In contrast, genes under genetic control are under relaxed constraint. Together, we demonstrate the distinct roles of aging and genetics on expression phenotypes. Age is a risk factor for many diseases, but the impact of aging on molecular phenotypes is not fully understood. Here, the authors quantify the relative contributions of genetics and aging to gene expression patterns across 27 tissues in humans, showing that age and genetics each play distinct roles in shaping expression phenotypes.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
4.3
作者：
Stegle O;Parts L;Durbin R;Winn J
通讯作者：
Winn J
影响因子：
7
作者：
Jia K;Cui C;Gao Y;Zhou Y;Cui Q
通讯作者：
Cui Q