Genetic and clinical determinants of telomere length

Allaire, Patrick D.; He, Jianxing; Mayer, John E.; Moat, Luke; Gerstenberger, Peter; Wilhorn, Reynor; Strutz, Sierra; Kim, David S.L.; Zenge, Chenji; Cox, Nancy J.; Shay, Jerry W.; Denny, Joshua C.; Bastarache, Lisa; Hebbring, Scott J.

doi:10.1016/j.xhgg.2023.100201

Cited by 9 publications

(6 citation statements)

References 64 publications

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“…We comprehensively examined the bidirectional causal relationships between LTL and complex traits, diseases, and lifestyle factors and used MVMR to examine causal effect mediation. Our study reiterates age and sex as major determinants of LTL variability [41, 18] and while hormonal and lifestyle variations showed different associations between males and females, they could not account for the observed sex differences. Still, the fact that lifestyle factors causally affect LTL emphasizes their influence on aging at a physiological and molecular level.…”

Section: Discussionmentioning

confidence: 59%

“…Recently, efforts to assess leukocyte telomere length (LTL) in large population biobanks have allowed comprehensive exploration of its relationships with lifestyle factors and health outcomes. Performing an LTL phenome-wide association study in 62,271 participants from the Vanderbilt University and Marshfield Clinic biobanks, Allaire et al ., identified associations with 67 phenotypes and showed that both shorter and longer telomeres associated with increased mortality [18]. Release of LTL measurements for ∼500,000 UK Biobank (UKBB) participants [19] and the companion first large-scale telomere length genome-wide association study (GWAS) [20] prompted investigation of the impact of LTL on hundreds of traits using phenome-wide Mendelian randomization (MR) [20, 21].…”

Section: Introductionmentioning

confidence: 99%

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Breaking down causes, consequences, and mediating effects of age-related telomere shortening on human health

Moix,

Sadler,

Kutalik

et al. 2024

Preprint

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Telomeres represent repeated DNA sequences at the ends of chromosomes, which shorten with each cell division. Factors modulating telomere attrition and the health consequences thereof are not fully understood. To address this, we leveraged data from 326,363 unrelated UK Biobank participants of European ancestry and used linear regression and bidirectional univariable and multivariable Mendelian randomization (MR and MVMR) to elucidate the relationships between leukocyte telomere length (LTL) and 141 complex traits, including diseases, biomarkers, and lifestyle factors. We confirm that telomeres shorten with age and show a stronger decline in males than in females, which cannot be explained by hormonal or lifestyle differences. MR revealed 23 traits modulating LTL; e.g., smoking cessation and high educational attainment associated with longer LTL, while weekly alcohol intake, body mass index, urate levels, and female reproductive events, such as childbirth, associated with shorter LTL. We also identified 26 traits affected by LTL, with risk for cardiovascular, pulmonary, renal, and some autoimmune diseases being increased by short LTL, while longer LTL increased risk for other autoimmune conditions and cancers. Through MVMR, we show that LTL partially mediates the impact of educational attainment, body mass index, and female age at childbirth on lifespan. These results provide new insights into the biology of telomere regulation by shedding light on the modulators, consequences, and the mediatory role of telomere shortening, portraying an intricate relationship between LTL, diseases, lifestyle, and socio-economic factors.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Breaking down causes, consequences, and mediating effects of age-related telomere shortening on human health

Moix,

Sadler,

Kutalik

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Telomere dynamics are influenced by genetic and environmental factors including nutritional intake and dietary habits. Genotype/phenotype analysis reveals genetic variations associated not only with metabolism but also expands to telomere length and integrity ( 75 ). Thus, an athlete's genetic makeup offers insights into their cellular aging pattern and potential effects on performance and longevity.…”

Section: Discussionmentioning

confidence: 99%

Advancing athletic assessment by integrating conventional methods with cutting-edge biomedical technologies for comprehensive performance, wellness, and longevity insights

Spanakis,

Fragkiadaki,

Renieri

et al. 2024

Front. Sports Act. Living

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In modern athlete assessment, the integration of conventional biochemical and ergophysiologic monitoring with innovative methods like telomere analysis, genotyping/phenotypic profiling, and metabolomics has the potential to offer a comprehensive understanding of athletes' performance and potential longevity. Telomeres provide insights into cellular functioning, aging, and adaptation and elucidate the effects of training on cellular health. Genotype/phenotype analysis explores genetic variations associated with athletic performance, injury predisposition, and recovery needs, enabling personalization of training plans and interventions. Metabolomics especially focusing on low-molecular weight metabolites, reveal metabolic pathways and responses to exercise. Biochemical tests assess key biomarkers related to energy metabolism, inflammation, and recovery. Essential elements depict the micronutrient status of the individual, which is critical for optimal performance. Echocardiography provides detailed monitoring of cardiac structure and function, while burnout testing evaluates psychological stress, fatigue, and readiness for optimal performance. By integrating this scientific testing battery, a multidimensional understanding of athlete health status can be achieved, leading to personalized interventions in training, nutrition, supplementation, injury prevention, and mental wellness support. This scientifically rigorous approach hereby presented holds significant potential for improving athletic performance and longevity through evidence-based, individualized interventions, contributing to advances in the field of sports performance optimization.

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“…The relative increase in redundance from v1.2 and phecodeX does not alter the basic statistics or interpretation of PheWAS. Indeed, researchers have developed methods to help identify primary versus secondary PheWAS associations ( Karnes et al 2017 , Allaire et al 2023 ). Third, phecodeX excludes injury and trauma phecodes that are present in v1.2.…”

Section: Limitationsmentioning

confidence: 99%

Next-generation phenotyping: introducing phecodeX for enhanced discovery research in medical phenomics

Shuey,

Stead,

Aka

et al. 2023

Bioinformatics

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Motivation Phecodes are widely used and easily adapted phenotypes based on International Classification of Diseases codes. The current version of phecodes (v1.2) was designed primarily to study common/complex diseases diagnosed in adults; however, there are numerous limitations in the codes and their structure. Results Here, we present phecodeX, an expanded version of phecodes with a revised structure and 1,761 new codes. PhecodeX adds granularity to phenotypes in key disease domains that are under-represented in the current phecode structure—including infectious disease, pregnancy, congenital anomalies, and neonatology—and is a more robust representation of the medical phenome for global use in discovery research. Availability and implementation phecodeX is available at https://github.com/PheWAS/phecodeX.

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Genetic and clinical determinants of telomere length

Cited by 9 publications

References 64 publications

Breaking down causes, consequences, and mediating effects of age-related telomere shortening on human health

Breaking down causes, consequences, and mediating effects of age-related telomere shortening on human health

Advancing athletic assessment by integrating conventional methods with cutting-edge biomedical technologies for comprehensive performance, wellness, and longevity insights

Next-generation phenotyping: introducing phecodeX for enhanced discovery research in medical phenomics

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