Biology subjects

Pierce, B. L.

Publications and source records attributed to Pierce, B. L..

7 recordsLinked to original sources

bioRxiv2026

Erythrocyte Count and the Human Natural Lifespan Limit: Evidence from the Long Life Family Study

Erythropoiesis is the most replication-intensive process in the body. Its lifelong replicative demands may erode hematopoietic cells replicative capacity, leading to a decline in erythrocyte count (EC) in older adults and limiting their lifespan. We examined the relationship between EC and mortality among 1,620 participants aged [≥]70 years in the Long Life Family Study and found that lower EC further augmented the exponential, age-dependent rise in mortality. We identified an EC threshold (ECT) (3.8x1012/L) below which mortality was amplified (p=9.3x10-6). As EC declined with age (p=8.2x10-18), it fell below this threshold in many participants, sharply increasing their mortality risk. This mortality-based ECT emerged from modeling, independent of the World Health Organization anemia definition, which is based on statistical thresholds (5th centiles) of hemoglobin distribution in populations [≤] 65 years. Thus, declining EC may be one of the biological factors imposing a natural lifespan limit on many older adults.

physiology↗

bioRxiv2020

Ten-year projection of white-nose syndrome disease dynamics at the southern leading-edge of infection in North America

Predicting the emergence and spread of infectious diseases is critical for effective conservation of biodiversity. White-nose syndrome (WNS), an emerging infectious disease of bats, has resulted in high mortality in eastern North America. Because the fungal causative agent Pseudogymnoascus destructans is constrained by temperature and humidity, spread dynamics may vary greatly by geography. Environmental conditions in the southern part of the continent, where disease dynamics are typically studied, making it difficult to predict how the disease will manifest. Herein, we modeled the spread of WNS in Texas based on available cave densities and average dispersal distances of species occupying these sites, and projected these results out to 10 years. We parameterized a predictive model of WNS epidemiology and its effects on hibernatory bat populations with observed environmental data from bat hibernation sites in Texas. Our model suggests that bat populations in northern Texas will be more affected by WNS mortality than southern Texas. As such, we recommend prioritizing the preservation of large overwintering colonies of bats in north Texas through management actions. Our model further illustrates that infectious disease spread and infectious disease severity can become uncoupled over a gradient of environmental variation. Finally, our results highlight the importance of understanding host, pathogen and environmental conditions in various settings to elucidate what may happen across a breadth of environments.

ecology↗

bioRxiv2020

Secondhand homes: Woodpecker cavity location and structure influences secondary nester's success.

O_LIUnderstanding how ecosystem engineers influence other organisms has long been a goal of ecologists. Woodpeckers select nesting sites with high food availability and will excavate and then abandon multiple cavities through their lifetime. These cavities are crucial to secondary cavity nesting birds (SCB) that are otherwise limited by the availability of naturally occurring cavities. C_LIO_LIOur study examined the role food resources have on the nest site location and home range size of woodpeckers, and the respective influence woodpeckers and the construction of cavities have on the nesting success of SCB. C_LIO_LIUsing five years of avian point count data to locate golden-fronted woodpeckers (GFWO: Melanerpes aurifrons), we correlated insect availability with GFWO home range size and determined differences in insect availability between GFWO occupied and unoccupied sites, while recording nesting success (success: [≥] 1 fledgling) for the GFWO and common SCB in south Texas: Black-crested Titmouse (Baeolophus atricristatus), Ash-throated Flycatcher (Myiarchus cinerascens), Brown-crested Flycatcher (Myiarchus tyrannulus), and Bewicks Wren (Thryomanes bewickii). We used model averaging to fit species-specific logistic regression models to predict nest success based on cavity metrics across all species. C_LIO_LISites occupied by GFWO had a higher biomass of insects in orders Coleoptera, Hymenoptera, and Orthoptera than unoccupied sites, and there was a negative correlation between the availability of these insect orders and home-range size. GFWO had increased nest success in trees with increased vegetation cover and lower levels of decay, while SCB had higher levels of nesting success in abandoned GFWO cavities opposed to naturally occurring ones, and in trees with low decay. C_LIO_LIOur results suggest that SCB may be drawn to nest in abandoned woodpecker cavities where they have higher rates of nest success compared to natural cavities. Additionally, the prevalence for GFWO to excavate cavities in trees with lower levels of decay contradicts previous literature and may indicate a novel temperature trade-off, with live trees requiring more energy to excavate, but providing more protection from high breeding season temperatures in arid and semi-arid areas. C_LI

ecology↗

bioRxiv2019

CCmed: cross-condition mediation analysis for identifying robust trans-eQTLs and assessing their effects on human traits

Trans-eQTLs collectively explain a substantial proportion of expression variation, yet are challenging to detect and replicate since their effects are individually weak. Many trans-effects are mediated by cis-gene expression and some of those effects are shared across tissue types/conditions. To detect robust cis-mediated trans-associations at the gene-level and for specific single nucleotide polymorphisms (SNPs), we proposed two Cross-Condition Mediation methods - CCmedgene and CCmedGWAS, respectively. We analyzed data from 13 brain tissue types from the Genotype-Tissue Expression (GTEx) project, and identified trios with cis-eQTLs of a cis-gene having associations with a trans-gene, many of which show evidence of replication in other datasets. By applying CCmedGWAS, we identified trans-genes associated with known schizophrenia susceptibility loci. We further conducted validation analyses assessing the schizophrenia-risk-associations of the identified trans-genes, by harnessing GWAS summary statistics from the Psychiatric Genomics Consortium and multitissue eQTL statistics from GTEx.

genetics↗

bioRxiv2019

Determinants of telomere length across human tissues

Telomere shortening is a hallmark of aging. Telomere length (TL) in blood cells has been studied extensively as a biomarker of human aging and disease; however, little is known regarding variability in TL in non-blood, disease-relevant tissue types. Here we characterize variability in TL measurements for 6,391 tissue samples, representing >20 tissue types and 952 individuals from the Genotype-Tissue Expression (GTEx) Project. We describe differences across tissue types, positive correlation among tissue types, and associations with age and ancestry. We show that genetic variation impacts TL in multiple tissue types, and that TL can mediate the effect of age on gene expression. Our results provide the foundational knowledge regarding TL in healthy tissues that is needed to interpret epidemiological studies of TL and human health.\n\nONE SENTENCE SUMMARYTelomere length varies by tissue type but is generally correlated among tissue types (positively) and with age (negatively).

genetics↗

bioRxiv2019

Genetically Increased Telomere Length and Aging-related Physical and Cognitive Traits in the UK Biobank

BackgroundTelomere length (TL) shortens over time in most human cell types and is a potential biomarker aging. However, the causal impact of TL on physical and cognitive phenotypes that decline with age has not been extensively examined. Using a Mendelian randomization (MR) approach, we utilized genetically increased TL (GI-TL) to estimate the impact of TL on aging-related traits among UK Biobank (UKB) participants. MethodsWe manually curated >50 aging-related traits from UKB and restricted to unrelated participants of British ancestry (n=337,522). We estimated GI-TL as a linear combination of nine TL-associated SNPs, each weighted by its previously-reported association with leukocyte TL. Regression models were used to assess the associations between GI-TL and each trait. We obtained MR estimates using the two-sample inverse variance weighted (IVW) approach. ResultsWe identified 5 age-related traits associated with GI-TL (Bonferroni-corrected threshold p<0.001): pulse pressure (PP) (p=5.2x10-14), systolic blood pressure (SBP) (p=2.9x10-15), diastolic blood pressure (DBP) (p=5.5x10-6), forced expiratory volume (FEV1) (p= p=0.0001), and forced vital capacity (FVC) (p=3.8x10-6). Under MR assumptions, one standard deviation increase in TL ([~]1200 base pairs) increased PP, SBP, and DBP by 1.5, 2.3, and 0.8 mmHg, respectively, while FEV1 and FVC increased by 34.7 and 52.2 mL, respectively. The observed associations appear unlikely to be due to selection bias based on analyses including inverse probability weights and analyses of simulated data. ConclusionsThese findings suggest that longer TL increases pulmonary function and blood pressure traits. Further research is necessary to evaluate TL in cardiovascular and pulmonary age-related decline. KEY MESSAGESO_LITelomere length (TL) is a potential biomarker and cause of aging, however, the causal relationship between TL and aging-related traits has not been thoroughly examined using a Mendelian randomization (MR) approach. C_LIO_LIWe evaluated genetically increased TL (GI-TL) and its association with over 50 aging-related traits in the UK Biobank cohort using regression models and MR approaches. C_LIO_LIPulmonary function (FEV1 and FVC) and blood pressure (SBP, DBP, and PP) traits were positively associated with GI-TL in the expected and unexpected direction, respectively. C_LIO_LIUsing inverse probability weights to account for the non-representativeness of the UKB, our observed associations for GI-TL with blood pressure traits and pulmonary function persisted. C_LIO_LIUsing simulated data to examine study selection as a potential source of collider bias, we concluded that selection bias was unlikely to explain the observed associations. C_LI

epidemiology↗

bioRxiv2018

The contribution of parent-to-offspring transmission of telomeres to the heritability of telomere length in humans

Leukocyte telomere length (LTL) is a heritable trait with two potential sources of heritability (h2): inherited variation in non-telomeric regions (e.g., SNPs that influence telomere maintenance) and variability in the lengths of telomeres in gametes that produce offspring zygotes (i.e., \"direct\" inheritance). Prior studies of LTL h2 have not attempted to disentangle these two sources. Here, we use a novel approach for detecting the direct inheritance of telomeres by studying the association between identity-by-descent (IBD) sharing at chromosome ends and phenotypic similarity in LTL. We measured genome-wide SNPs and LTL for a sample of 5,069 Bangladeshi adults with substantial relatedness. For each of the 7,254 relative pairs identified, we used SNPs near the telomeres to estimate the number of chromosome ends shared IBD, a proxy for the number of telomeres shared IBD (Tshared). We then estimated the association between Tshared and the squared pairwise difference in LTL (({Delta}LTL)2) within various classes of relatives (siblings, avuncular, cousins, and distant), adjusting for overall genetic relatedness ({phi}). The association between Tshared and ({Delta}LTL)2 was inverse among all relative pair types. In a meta-analysis including all relative pairs ({phi} >0.05), the association between Tshared and ({Delta}LTL)2 (P=0.002) was stronger than the association between {phi} and ({Delta}LTL)2 (P=0.45). Our results provide strong evidence that telomere length (TL) in parental germ cells impacts TL in offspring cells and contributes to LTL h2 despite telomere \"reprogramming\" during embryonic development. Applying our method to larger studies will enable robust estimation of LTL h2 attributable to direction transmission.

genetics↗