Genetic interplay between human longevity and metabolic pathways — a large‐scale eQTL study

Summary Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic factors to longevity is a challenging task. Here, we conducted a large‐scale RNA‐sequencing‐based expression quantitative trait loci study (eQTL) w...

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Published inAging cell Vol. 16; no. 4; pp. 716 - 725
Main Authors Häsler, Robert, Venkatesh, Geetha, Tan, Qihua, Flachsbart, Friederike, Sinha, Anupam, Rosenstiel, Philip, Lieb, Wolfgang, Schreiber, Stefan, Christensen, Kaare, Christiansen, Lene, Nebel, Almut
Format Journal Article
LanguageEnglish
Published England John Wiley & Sons, Inc 01.08.2017
John Wiley and Sons Inc
Subjects
Adult
Aged
Aged, 80 and over
Analysis
Denmark
functional genomics
Genes
Genetic aspects
Genetic research
Genetic transcription
Genome, Human
Genotype
Germany
Heritability
High-Throughput Nucleotide Sequencing
human
Humans
Longevity
Longevity - genetics
Longitudinal Studies
Metabolic Networks and Pathways - genetics
Metabolic pathways
Metabolism
Middle Aged
Original
Physiological aspects
Polymorphism, Single Nucleotide
Quantitative genetics
Quantitative Trait Loci
Quantitative Trait, Heritable
Ribonucleic acid
RNA
RNA sequencing
Transcription
Transcriptome
Twins
Twins, Dizygotic
Twins, Monozygotic
longevity
functional genomics
RNA- sequencing
human
transcriptome
Online AccessGet full text

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Abstract Summary Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic factors to longevity is a challenging task. Here, we conducted a large‐scale RNA‐sequencing‐based expression quantitative trait loci study (eQTL) with subsequent heritability analysis. The investigation was performed on blood samples from 244 individuals from Germany and Denmark, representing various age groups including long‐lived subjects up to the age of 104 years. Our eQTL‐based approach revealed for the first time that human longevity is associated with a depletion of metabolic pathways in a genotype‐dependent and independent manner. Further analyses indicated that 20% of the differentially expressed genes are influenced by genetic variants in cis. The subsequent study of twins showed that the transcriptional activity of a third of the differentially regulated genes is heritable. These findings suggest that longevity‐associated biological processes such as altered metabolism are, to a certain extent, also the driving force of longevity rather than just a consequence of old age.
AbstractList Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic factors to longevity is a challenging task. Here, we conducted a large-scale RNA-sequencing-based expression quantitative trait loci study (eQTL) with subsequent heritability analysis. The investigation was performed on blood samples from 244 individuals from Germany and Denmark, representing various age groups including long-lived subjects up to the age of 104 years. Our eQTL-based approach revealed for the first time that human longevity is associated with a depletion of metabolic pathways in a genotype-dependent and independent manner. Further analyses indicated that 20% of the differentially expressed genes are influenced by genetic variants in cis. The subsequent study of twins showed that the transcriptional activity of a third of the differentially regulated genes is heritable. These findings suggest that longevity-associated biological processes such as altered metabolism are, to a certain extent, also the driving force of longevity rather than just a consequence of old age.
Summary Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic factors to longevity is a challenging task. Here, we conducted a large‐scale RNA‐sequencing‐based expression quantitative trait loci study (eQTL) with subsequent heritability analysis. The investigation was performed on blood samples from 244 individuals from Germany and Denmark, representing various age groups including long‐lived subjects up to the age of 104 years. Our eQTL‐based approach revealed for the first time that human longevity is associated with a depletion of metabolic pathways in a genotype‐dependent and independent manner. Further analyses indicated that 20% of the differentially expressed genes are influenced by genetic variants in cis. The subsequent study of twins showed that the transcriptional activity of a third of the differentially regulated genes is heritable. These findings suggest that longevity‐associated biological processes such as altered metabolism are, to a certain extent, also the driving force of longevity rather than just a consequence of old age.
Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic factors to longevity is a challenging task. Here, we conducted a large‐scale RNA ‐sequencing‐based expression quantitative trait loci study ( eQTL ) with subsequent heritability analysis. The investigation was performed on blood samples from 244 individuals from Germany and Denmark, representing various age groups including long‐lived subjects up to the age of 104 years. Our eQTL ‐based approach revealed for the first time that human longevity is associated with a depletion of metabolic pathways in a genotype‐dependent and independent manner. Further analyses indicated that 20% of the differentially expressed genes are influenced by genetic variants in cis . The subsequent study of twins showed that the transcriptional activity of a third of the differentially regulated genes is heritable. These findings suggest that longevity‐associated biological processes such as altered metabolism are, to a certain extent, also the driving force of longevity rather than just a consequence of old age.
Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic factors to longevity is a challenging task. Here, we conducted a large-scale RNA-sequencing-based expression quantitative trait loci study (eQTL) with subsequent heritability analysis. The investigation was performed on blood samples from 244 individuals from Germany and Denmark, representing various age groups including long-lived subjects up to the age of 104 years. Our eQTL-based approach revealed for the first time that human longevity is associated with a depletion of metabolic pathways in a genotype-dependent and independent manner. Further analyses indicated that 20% of the differentially expressed genes are influenced by genetic variants in cis. The subsequent study of twins showed that the transcriptional activity of a third of the differentially regulated genes is heritable. These findings suggest that longevity-associated biological processes such as altered metabolism are, to a certain extent, also the driving force of longevity rather than just a consequence of old age.Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic factors to longevity is a challenging task. Here, we conducted a large-scale RNA-sequencing-based expression quantitative trait loci study (eQTL) with subsequent heritability analysis. The investigation was performed on blood samples from 244 individuals from Germany and Denmark, representing various age groups including long-lived subjects up to the age of 104 years. Our eQTL-based approach revealed for the first time that human longevity is associated with a depletion of metabolic pathways in a genotype-dependent and independent manner. Further analyses indicated that 20% of the differentially expressed genes are influenced by genetic variants in cis. The subsequent study of twins showed that the transcriptional activity of a third of the differentially regulated genes is heritable. These findings suggest that longevity-associated biological processes such as altered metabolism are, to a certain extent, also the driving force of longevity rather than just a consequence of old age.
Summary Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic factors to longevity is a challenging task. Here, we conducted a large-scale RNA-sequencing-based expression quantitative trait loci study (eQTL) with subsequent heritability analysis. The investigation was performed on blood samples from 244 individuals from Germany and Denmark, representing various age groups including long-lived subjects up to the age of 104 years. Our eQTL-based approach revealed for the first time that human longevity is associated with a depletion of metabolic pathways in a genotype-dependent and independent manner. Further analyses indicated that 20% of the differentially expressed genes are influenced by genetic variants in cis. The subsequent study of twins showed that the transcriptional activity of a third of the differentially regulated genes is heritable. These findings suggest that longevity-associated biological processes such as altered metabolism are, to a certain extent, also the driving force of longevity rather than just a consequence of old age.
Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic factors to longevity is a challenging task. Here, we conducted a large-scale RNA-sequencing-based expression quantitative trait loci study (eQTL) with subsequent heritability analysis. The investigation was performed on blood samples from 244 individuals from Germany and Denmark, representing various age groups including long-lived subjects up to the age of 104 years. Our eQTL-based approach revealed for the first time that human longevity is associated with a depletion of metabolic pathways in a genotype-dependent and independent manner. Further analyses indicated that 20% of the differentially expressed genes are influenced by genetic variants in cis. The subsequent study of twins showed that the transcriptional activity of a third of the differentially regulated genes is heritable. These findings suggest that longevity-associated biological processes such as altered metabolism are, to a certain extent, also the driving force of longevity rather than just a consequence of old age.
Audience Academic
Author Venkatesh, Geetha
Nebel, Almut
Sinha, Anupam
Christiansen, Lene
Schreiber, Stefan
Rosenstiel, Philip
Flachsbart, Friederike
Häsler, Robert
Tan, Qihua
Lieb, Wolfgang
Christensen, Kaare
AuthorAffiliation 2 The Danish Twin Registry Unit of Epidemiology, Biostatistics and Biodemography University of Southern Denmark 5000 Odense Denmark
4 Institute of Epidemiology Kiel University 24105 Kiel Germany
1 Institute of Clinical Molecular Biology Kiel University 24105 Kiel Germany
3 Department of Clinical Genetics Odense University Hospital 5000 Odense Denmark
5 Department of Clinical Biochemistry and Pharmacology Odense University Hospital 5000 Odense Denmark
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Keywords longevity
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human
transcriptome
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Snippet Summary Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic...
Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic factors to...
Summary Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic...
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pubmed
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StartPage 716
SubjectTerms Adult
Aged
Aged, 80 and over
Analysis
Denmark
functional genomics
Genes
Genetic aspects
Genetic research
Genetic transcription
Genome, Human
Genotype
Germany
Heritability
High-Throughput Nucleotide Sequencing
human
Humans
Longevity
Longevity - genetics
Longitudinal Studies
Metabolic Networks and Pathways - genetics
Metabolic pathways
Metabolism
Middle Aged
Original
Physiological aspects
Polymorphism, Single Nucleotide
Quantitative genetics
Quantitative Trait Loci
Quantitative Trait, Heritable
Ribonucleic acid
RNA
RNA sequencing
Transcription
Transcriptome
Twins
Twins, Dizygotic
Twins, Monozygotic
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Title Genetic interplay between human longevity and metabolic pathways — a large‐scale eQTL study
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Facel.12598
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Volume 16
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