Publications by authors named "Peter Joshi"
An expert consensus statement on biomarkers of ageing for use in intervention studies.
J Gerontol A Biol Sci Med Sci
December 2024
Biomarkers of ageing serve as important outcome measures in longevity-promoting interventions. However, there is limited consensus on which specific biomarkers are most appropriate for human intervention studies. This work aimed to address this need by establishing an expert consensus on biomarkers of ageing for use in intervention studies via the Delphi method.
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- Genetic studies have highlighted the need for more diverse research on plasma fibrinogen levels, as previous studies largely focused on Europeans, leading to gaps in understanding and missing heritability.
- By analyzing data from whole-genome sequencing and genotype data from large cohorts, researchers identified 18 genetic loci related to fibrinogen levels, some of which are more common in African populations and include variants that may impact protein function.
- The study's findings indicate a connection between fibrinogen levels and various health conditions, emphasizing the importance of whole-genome sequencing in discovering genetic factors in diverse populations and enhancing knowledge about fibrinogen regulation.
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- Scientists looked at the timing of when girls start their periods (called menarche) and how it can affect their health later in life.
- They studied about 800,000 women and found over a thousand genetic signals that influence when menstruation starts.
- Some women have a much higher chance of starting their periods too early or too late based on their genetic makeup, suggesting that genes play a big role in this process!
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- - This study conducted a genome-wide association analysis on metabolic traits in over 136,000 participants, revealing over 400 genetic loci that influence human metabolism and complex diseases.
- - Researchers used advanced techniques like nuclear magnetic resonance spectroscopy to link specific genetic variants with how they affect lipoprotein metabolism and other metabolic processes.
- - The findings highlight the genetic connections between metabolism and conditions such as hypertension, providing valuable data for further research on metabolic-related diseases.
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- * Discovery of 7 new genetic loci associated with FVIII and 1 new locus for VWF, supporting their roles in thrombotic outcomes via Mendelian randomization.
- * Functional testing revealed that silencing genes like B3GNT2 and CD36 impacted FVIII and VWF release from endothelial cells, indicating their potential regulatory roles.
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- X-chromosomal genetic variants can provide important information about differences in human traits and diseases between sexes.
- A large-scale study analyzed kidney-related traits in nearly 909,000 individuals, finding 23 genetic loci linked to uric acid levels and estimated glomerular filtration rate (eGFR), including four new genes that may play a role in kidney function.
- The research also discovered five novel sex-specific interactions, with variations showing different effects in males and females, and highlighted genes that are responsive to androgens (male hormones), indicating a complex relationship between sex and kidney-related genetics.
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- Biological age is a better indicator of health than chronological age and can be estimated using blood-based biomarkers; this study focuses on improving this estimation with machine learning.
- Using data from over 306,000 participants, researchers developed an Elastic-Net Cox model that predicts mortality risk, achieving a higher predictive accuracy than a popular existing model (PhenoAge).
- The study concludes that a practical method for estimating biological age, which can vary significantly from chronological age, is feasible and can be made accessible to the general public through common clinical assays.
Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans).
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- Human plasma proteins are crucial as clinical biomarkers and potential drug targets, and studying their genetic variants can help us understand their abundance.
- The study conducted a meta-analysis across nearly 23,000 individuals to identify genetic variants associated with 92 plasma proteins linked to cardiometabolic conditions, discovering 503 significant variants.
- Notably, sex differences were observed in 23.5% of the identified variants, and further analysis suggested causal links between certain proteins and various health traits, providing insight into their roles in cardiometabolic diseases.
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- This study examines the relationship between resting heart rate and cardiovascular diseases, identifying 493 genetic variants linked to this trait through a large-scale analysis of 835,465 individuals.
- It highlights the significance of higher genetically predicted resting heart rates, which are associated with an increased risk of dilated cardiomyopathy but lower risk for conditions like atrial fibrillation and ischemic strokes.
- The study also challenges previous findings on resting heart rate and all-cause mortality, suggesting earlier results may have been influenced by biases, ultimately enhancing our understanding of the biological implications of resting heart rate in cardiovascular health.
Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively.
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- Genetic studies on plasma fibrinogen levels primarily focused on Europeans, revealing numerous associated regions, but there are gaps in understanding due to missing heritability and representation of non-Europeans.
- The researchers utilized whole genome sequencing (WGS) and array-based genotyping data from large cohorts to identify 18 new genetic loci linked to fibrinogen levels, with some variants more common in African populations.
- The study highlights the importance of WGS in discovering genetic variations across diverse populations, linking fibrinogen polygenic risk scores to increased risk for thrombotic and inflammatory diseases like gout.
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- A major study involving 580,869 participants identified 1,020 genetic signals linked to lung function impairment, which is crucial in understanding chronic obstructive pulmonary disease (COPD) and predicting mortality.
- * The research found 559 genes related to lung function that were connected to 29 different biological pathways and demonstrated variations across ancestry, age, and smoking habits.
- * Findings suggest potential new targets for therapy by highlighting specific genetic variants and proteins, ultimately contributing to better understanding and treatment of COPD.
Obesity remains an unmet global health burden. Detrimental anatomical distribution of body fat is a major driver of obesity-mediated mortality risk and is demonstrably heritable. However, our understanding of the full genetic contribution to human adiposity is incomplete, as few studies measure adiposity directly.
View Article and Find Full Text PDFBackground: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.
Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.
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- Common SNPs may account for 40-50% of human height variation, and this study identifies 12,111 SNPs linked to height from a large sample of 5.4 million individuals.
- These SNPs cluster in 7,209 genomic segments, encompassing about 21% of the genome and showing varying densities enriched in relevant genes.
- While these SNPs explain a substantial portion of height variance in European populations (40-45%), their predictive power is lower (10-24%) in other ancestries, suggesting a need for more research to enhance understanding in diverse populations.
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- - The study analyzed data from 703,901 individuals and identified 99 genetic loci related to physical activity levels and sedentary behavior, particularly focusing on leisure time activities and screen use.
- - Certain genes linked to sedentary behavior show heightened expression in skeletal muscle when influenced by resistance training, highlighting a connection between genetics and exercise.
- - The findings suggest that lower screen time and increased physical activity can positively impact health, but these effects may be influenced by factors like body mass index (BMI).
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- Understanding the genetic basis of memory could help address neurodegenerative disorders, and a study examined this in a large group of adults without dementia or stroke (N=53,637).
- Researchers identified new genetic locations associated with verbal short-term memory and learning, particularly in the genes CDH18 and APOE/APOC1/TOMM40, with results verified in a separate sample.
- Analysis showed that a genetic score for verbal learning correlated with brain activity during memory tasks and linked memory traits to various cognitive and health outcomes.
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- Researchers studied the genetic connections to blood fats using data from 1.6 million people from different backgrounds to understand why certain fats are higher or lower in the body.
- They looked at special genes and how they interact in the liver and fat cells, finding that the liver plays a big part in controlling fat levels.
- Two specific genes, CREBRF and RRBP1, were highlighted as important in understanding how our bodies manage fats due to strong supporting evidence.
Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA HOTAIR (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with polycomb repressive complex 2 (PRC2) and we identify core HOTAIR-PRC2 target genes involved in adipocyte lineage determination.
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