Genetic interplay between human longevity and metabolic pathways

a large-scale eQTL study

Robert Häsler, Geetha Venkatesh, Qihua Tan, Friederike Flachsbart, Anupam Sinha, Philip Rosenstiel, Wolfgang Lieb, Stefan Schreiber, Kaare Christensen, Lene Christiansen, Almut Nebel*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.

Original languageEnglish
JournalAging Cell
Volume16
Issue number4
Pages (from-to)716–725
ISSN1474-9718
DOIs
Publication statusPublished - 2017

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Quantitative Trait Loci
Metabolic Networks and Pathways
RNA Sequence Analysis
Twin Studies
Denmark
Germany
Age Groups

Keywords

  • Functional genomics
  • Human
  • Longevity
  • RNA- sequencing
  • Transcriptome

Cite this

Häsler, R., Venkatesh, G., Tan, Q., Flachsbart, F., Sinha, A., Rosenstiel, P., ... Nebel, A. (2017). Genetic interplay between human longevity and metabolic pathways: a large-scale eQTL study. Aging Cell, 16(4), 716–725. https://doi.org/10.1111/acel.12598
Häsler, Robert ; Venkatesh, Geetha ; Tan, Qihua ; Flachsbart, Friederike ; Sinha, Anupam ; Rosenstiel, Philip ; Lieb, Wolfgang ; Schreiber, Stefan ; Christensen, Kaare ; Christiansen, Lene ; Nebel, Almut. / Genetic interplay between human longevity and metabolic pathways : a large-scale eQTL study. In: Aging Cell. 2017 ; Vol. 16, No. 4. pp. 716–725.
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Häsler, R, Venkatesh, G, Tan, Q, Flachsbart, F, Sinha, A, Rosenstiel, P, Lieb, W, Schreiber, S, Christensen, K, Christiansen, L & Nebel, A 2017, 'Genetic interplay between human longevity and metabolic pathways: a large-scale eQTL study', Aging Cell, vol. 16, no. 4, pp. 716–725. https://doi.org/10.1111/acel.12598

Genetic interplay between human longevity and metabolic pathways : a large-scale eQTL study. / Häsler, Robert; Venkatesh, Geetha; Tan, Qihua; Flachsbart, Friederike; Sinha, Anupam; Rosenstiel, Philip; Lieb, Wolfgang; Schreiber, Stefan; Christensen, Kaare; Christiansen, Lene; Nebel, Almut.

In: Aging Cell, Vol. 16, No. 4, 2017, p. 716–725.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Genetic interplay between human longevity and metabolic pathways

T2 - a large-scale eQTL study

AU - Häsler, Robert

AU - Venkatesh, Geetha

AU - Tan, Qihua

AU - Flachsbart, Friederike

AU - Sinha, Anupam

AU - Rosenstiel, Philip

AU - Lieb, Wolfgang

AU - Schreiber, Stefan

AU - Christensen, Kaare

AU - Christiansen, Lene

AU - Nebel, Almut

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AB - 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.

KW - Functional genomics

KW - Human

KW - Longevity

KW - RNA- sequencing

KW - Transcriptome

U2 - 10.1111/acel.12598

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JO - Aging Cell

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SN - 1474-9718

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