Demographic History Research Articles

Forest genomics in the Caucasus through the lens of its dominant tree species - Fagus orientalis.

The last glacial period is known to have greatly influenced the demographic history of temperate forest trees, with important range contractions and post-glacial expansions that led to the formation of multiple genetic lineages and secondary contact zones in the Northern Hemisphere. These dynamics have been extensively studied for European and North American species but are still poorly understood in other temperate regions of rich biodiversity such as the Caucasus. Our study helps filling that gap by deciphering the genomic landscapes of F. orientalis across the South Caucasus. The use of genome-wide data confirmed a past demographic history strongly influenced by the Last Glacial Maximum, revealing two disjunct glacial refugia in the Colchis and Hyrcanian regions. The resulting patterns of genetic diversity, load and differentiation are not always concordant across the region, with genetic load pinpointing the location of the glacial refugia more efficiently than genetic diversity alone. The Hyrcanian forests show depleted genetic diversity and substantial isolation, even if long-distance gene flow is still present with the main centre of diversity in the Greater Caucasus. Finally, we characterize a strong heterogeneity of genetic diversity and differentiation along the species chromosomes, with noticeably a first chromosome showing low diversity and weak differentiation.

Early-Life Disease Exposure and Its Heterogeneous Effects on Mortality Throughout Life: Sweden, 1905-2016.

Exposure to infectious diseases in early life has been linked to increased mortality risk in later life in high-disease settings, such as eighteenth- and nineteenth-century Europe. Less is known about the long-term effects of early-life disease exposure in milder disease environments. This study estimates heterogeneous effects from disease exposure in infancy on later-life mortality in twentieth-century Sweden, by socioeconomic status at birth and sex. Using historical population data for southern Sweden, we study 11,515 individuals who were born in 1905-1929 from age 1 until age 85. We measure exposure to disease using the local post-early neonatal mortality rate in the first 12 months after birth and apply flexible parametric survival models. For females, we find a negative effect on life expectancy (scarring) at ages 1-85 following high disease exposure in infancy, particularly for those born to unskilled workers. For males, we find no negative effect on later-life survival, likely because stronger mortality selection in infancy outweighs scarring. Thus, even as the incidence of infectious diseases declined at the start of the twentieth century, early-life disease exposure generated long-lasting negative but heterogeneous population health effects.

Duel of Germanists: The debate between Elemér Moór, Elemér Schwartz and Walter Steinhauser about the population history of Burgenland

Duel of Germanists: The debate between Elemér Moór, Elemér Schwartz and Walter Steinhauser about the population history of Burgenland

Climatic fluctuations, geographic features, and evolutionary forces: Shaping high genomic diversity and local adaptation in Muntiacus reevesi

AbstractAimGenetic diversity is crucial for species adaptability. Understanding the mechanisms behind its formation and maintenance is essential for effective conservation. Recent studies have demonstrated that despite experiencing severe population bottlenecks, Muntiacus reevesi retains high genetic diversity and continues its northward migration, indicative of ongoing adaptive evolution. However, our comprehension of this phenomenon remains incomplete. The objective of this study is to explore the mechanisms underlying the formation of high genetic diversity and the genomic characteristics associated with local adaptation, using M. reevesi as a case study.LocationSouthern China.MethodsWe analysed resequencing data from 62 genomes and identified 29,124,081 high‐quality single‐nucleotide polymorphisms (SNPs). We used population genetics, demographic history, population differentiation, gene flow analysis software, and genotype‐environment association (GEA) models to assess the factors that have contributed to high genetic diversity and environmental adaptability in the historical climate and geographical context.ResultsThe study identified that during Pleistocene climatic fluctuations, M. reevesi diverged into eastern (DB and WJW populations) and western lineages (WL, BA, and QL populations), all displayed high genetic diversity. Historically, M. reevesi maintained large effective populations, but contemporary human‐induced threats have led to a significant decline. Population differentiation models suggest distinct expansion pathways for eastern and western lineages, resulting in population admixture, with mountain corridors facilitating gene flow and maintaining high genetic diversity. Additionally, environmental‐genotype analysis revealed local adaptation in the QL‐BA population, highlighting candidate adaptive genes (ME3 and PRKG1) potentially linked to cold adaptation and foraging behaviour.ConclusionThis study enhances our understanding of the mechanisms behind the high genetic diversity and environmental adaptability of M. reevesi, offering insights into how bottleneck populations maintain diversity, crucial for biogeographic research and conservation strategies for similar species.

Ancestral origins and admixture history of Kazakhs.

Kazakh people, like many other populations that settled in Central Asia, demonstrate an array of mixed anthropological features of East Eurasian (EEA) and West Eurasian (WEA) populations, indicating a possible scenario of biological admixture between already differentiated EEA and WEA populations. However, their complex biological origin and genomic makeup, as well as their genetic interaction with surrounding populations, are not well understood. In an attempt to decipher their genetic structure and population history, we conducted, to our knowledge, the first whole-genome sequencing study of Kazakhs residing in Xinjiang (KZK). We demonstrated that KZK derived their ancestries from four ancestral source populations: East Asian (∼39.7%), West Asian (∼28.6%), Siberian (∼23.6%), and South Asian (∼8.1%). The recognizable interactions of EEA and WEA ancestries in Kazakhs were dated back to the 15th century BCE. Kazakhs were genetically distinctive from Uyghurs in terms of their overall genomic makeup, although the two populations were closely related in genetics, and both showed a substantial admixture of EEA and WEA ancestries. Notably, we identified a considerable sex-biased admixture, with an excess of western males and eastern females contributing to the KZK gene pool. We further identified a set of genes that showed remarkable differentiation in KZK from the surrounding populations, including those associated with skin color (SLC24A5, OCA2), essential hypertension (HLA-DQB1), hypertension (MTHFR, SLC35F3), and neuron development (CNTNAP2). These results advance our understanding of the complex history of contacts between Western and Eastern Eurasians, especially those situated along the old Silk Road.

Individual joints involvement pattern in psoriatic arthritis: A cross-sectional study in China.

Psoriatic arthritis (PsA) is characterized by multi-joint involvement, primarily affecting the small joints in the hands and feet. However, the specific pattern of joint involvement at an individual level remains uncertain. This study aimed to elucidate the pattern of joint involvement in a PsA cohort. Patients diagnosed with PsA were recruited for this cross-sectional study. Demographic, clinical, laboratory, personal and family history, and comorbidity data were collected. Descriptive statistical analysis was performed, and univariate and multivariate regression models were used to examine baseline factors influencing joint involvement. A total of 264 PsA patients (156 males) were included in the study. The results revealed a predominant involvement of peripheral facet joints. The second proximal interphalangeal joint (PIP) of the right hand exhibited the highest prevalence of swelling (18.9%), while the right knee joint had the highest prevalence of tenderness (24.2%). Older age and earlier onset of PsA were identified as independent factors associated with the swelling of the second PIP of the right hand. Older age, earlier onset of PsA, lower Psoriasis Area and Severity Index and higher Dermatology Life Quality Index scores were identified as independent factors associated with the tenderness of the right knee joint. In conclusion, the most commonly affected joints in PsA are the second PIP of the right hand and the right knee joint.

Elevated Baseline Mean Corpuscular Volume Predicts the Development of Severe Hematologic Toxicity After 177Lu-DOTATATE Therapy.

177Lu-DOTATATE is an effective second-line treatment for metastatic or nonresectable neuroendocrine tumors. This treatment can result in hematologic severe adverse reactions (SARs). Preemptive identification of patients at risk of SARs could mitigate this risk and improve treatment safety and outcomes. Methods: Demographic and oncologic history, pretreatment laboratory values, and SAR frequency were obtained for 126 sequential patients treated with 177Lu-DOTATATE. Univariable and multivariable logistic regression models identified factors correlating with SARs. Results: Relative pretreatment anemia, leukopenia, thrombocytopenia, and elevated mean corpuscular volume (MCV) were significantly correlated with SARs, with an odds ratio of 16 (95% CI, 5-65) in patients with an MCV greater than 95 fL. Conclusion: Pretreatment bone marrow dyscrasias, including an MCV greater than 95 fL, may predict patients at risk for SARs when treated with 177Lu-DOTATATE. Further study is needed to determine whether the risks of SARs outweigh the benefit in these patients.

Neonatal Outcomes after Maternal Biomarker-Guided Preterm Birth Intervention: The AVERT PRETERM Trial

The AVERT PRETERM trial (NCT03151330) evaluated whether screening clinically low-risk pregnancies with a validated maternal blood biomarker test for spontaneous preterm birth (sPTB) risk, followed by preventive treatments for those screening positive, would improve neonatal outcomes compared to a clinically low-risk historical population that had received the usual care. Prospective arm participants with singleton non-anomalous pregnancies and no PTB history were tested for sPTB risk at 191/7–206/7 weeks’ gestation and followed up with after neonatal discharge. Screen-positive individuals (≥16% sPTB risk) were offered vaginal progesterone (200 mg) and aspirin (81 mg) daily, with twice-weekly nurse phone calls. Co-primary outcomes were neonatal morbidity and mortality, measured using a validated composite index (NMI), and neonatal hospital length of stay (NNLOS). Endpoints were assessed using survival analysis and logistic regression in a modified intent-to-treat population comprising screen-negative individuals and screen-positive individuals accepting treatment. Of 1460 eligible participants, 34.7% screened positive; of these, 56.4% accepted interventions and 43.6% declined. Compared to historical controls, prospective arm neonates comprising mothers accepting treatment had lower NMI scores (odds ratio 0.81, 95% CI, 0.67–0.98, p = 0.03) and an 18% reduction in severe morbidity. NNLOS was shorter (hazard ratio 0.73, 95% CI, 0.58–0.92, p = 0.01), with a 21% mean stay decrease among neonates having the longest stays. Sensitivity analyses in the entire intent-to-treat population supported these findings. These results suggest that biomarker sPTB risk stratification and preventive interventions can ameliorate PTB complications in singleton, often nulliparous, pregnancies historically deemed low risk.

Neonatal Outcomes after Maternal Biomarker-Guided Preterm Birth Intervention: The AVERT PRETERM Trial

The AVERT PRETERM trial (NCT03151330) evaluated whether screening clinically low-risk pregnancies with a validated maternal blood biomarker test for spontaneous preterm birth (sPTB) risk, followed by preventive treatments for those screening positive, would improve neonatal outcomes compared to a clinically low-risk historical population that had received the usual care. Prospective arm participants with singleton non-anomalous pregnancies and no PTB history were tested for sPTB risk at 191/7–206/7 weeks’ gestation and followed up with after neonatal discharge. Screen-positive individuals (≥16% sPTB risk) were offered vaginal progesterone (200 mg) and aspirin (81 mg) daily, with twice-weekly nurse phone calls. Co-primary outcomes were neonatal morbidity and mortality, measured using a validated composite index (NMI), and neonatal hospital length of stay (NNLOS). Endpoints were assessed using survival analysis and logistic regression in a modified intent-to-treat population comprising screen-negative individuals and screen-positive individuals accepting treatment. Of 1460 eligible participants, 34.7% screened positive; of these, 56.4% accepted interventions and 43.6% declined. Compared to historical controls, prospective arm neonates comprising mothers accepting treatment had lower NMI scores (odds ratio 0.81, 95% CI, 0.67–0.98, p = 0.03) and an 18% reduction in severe morbidity. NNLOS was shorter (hazard ratio 0.73, 95% CI, 0.58–0.92, p = 0.01), with a 21% mean stay decrease among neonates having the longest stays. Sensitivity analyses in the entire intent-to-treat population supported these findings. These results suggest that biomarker sPTB risk stratification and preventive interventions can ameliorate PTB complications in singleton, often nulliparous, pregnancies historically deemed low risk.

Conservation genomics of the wild pumpkin Cucurbita radicans in Central Mexico: The influence of a changing environment on the genetic diversity and differentiation of a rare species.

The genetic diversity found in natural populations is the result of the evolutionary forces in response to historical and contemporary factors. The environmental characteristics and geological history of Mexico promoted the evolution and diversification of plant species, including wild relatives of crops such as the wild pumpkins (Cucurbita). Wild pumpkin species are found in a variety of habitats, evidencing their capability to adapt to different environments. Despite the potential value of wild Cucurbita as a genetic reservoir for crops, there is a lack of studies on their genetic diversity. Cucurbita radicans is an endangered species threatened by habitat destruction leading to low densities in small and isolated populations. Here, we analyze Genotype by Sequencing genomic data of the wild pumpkin C. radicans to evaluate the influence of factors like isolation, demographic history, and the environment shaping the amount and distribution of its genetic variation. We analyzed 91 individuals from 14 localities along its reported distribution. We obtained 5,107 SNPs and found medium-high levels of genetic diversity and genetic structure distributed in four main geographic areas with different environmental conditions. Moreover, we found signals of demographic growth related to historical climatic shifts. Outlier loci analysis showed significant association with the environment, principally with precipitation variables. Also, the outlier loci displayed differential changes in their frequencies in response to future global climate change scenarios. Using the results of genetic structure, outlier loci and multivariate analyses of the environmental conditions, we propose priority localities for conservation that encompass most of the genetic diversity of C. radicans.

Risk to reoffend changes over time: Improving correctional programming through progress monitoring.

Progress monitoring is integral to evidence-based practice. Correctional settings, especially the supervision of individuals who commit sexual offenses, elicit public concern; negative outcomes can be catastrophic. Using a prospective longitudinal study of 2,939 men with a history of sexual offenses undergoing community supervision, we examined different models of progress monitoring and how they should inform the assessment of risk for sexual recidivism. We found that the most recent assessment scores of the ACUTE-2007 and STABLE-2007 sexual recidivism risk tools provided the best information about reoffending risk compared to using (a) the worst period of adjustments (i.e., highest risk score), (b) the best period of adjustments (i.e., lowest risk score), or (c) a rolling average of scores. We also found that the latest STABLE-2007 scores incrementally predicted sexual recidivism beyond baseline risk as assessed by demographic and criminal history variables (Static-99R). We conclude that the risk for sexual recidivism changes over time and that community corrections is advanced by repeated assessment of dynamic (changeable) risk factors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Risk to reoffend changes over time: Improving correctional programming through progress monitoring.

Progress monitoring is integral to evidence-based practice. Correctional settings, especially the supervision of individuals who commit sexual offenses, elicit public concern; negative outcomes can be catastrophic. Using a prospective longitudinal study of 2,939 men with a history of sexual offenses undergoing community supervision, we examined different models of progress monitoring and how they should inform the assessment of risk for sexual recidivism. We found that the most recent assessment scores of the ACUTE-2007 and STABLE-2007 sexual recidivism risk tools provided the best information about reoffending risk compared to using (a) the worst period of adjustments (i.e., highest risk score), (b) the best period of adjustments (i.e., lowest risk score), or (c) a rolling average of scores. We also found that the latest STABLE-2007 scores incrementally predicted sexual recidivism beyond baseline risk as assessed by demographic and criminal history variables (Static-99R). We conclude that the risk for sexual recidivism changes over time and that community corrections is advanced by repeated assessment of dynamic (changeable) risk factors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Genetic diversity and connectivity of the invasive gastropod, Callinina georgiana (Caenogastropoda: Viviparidae) across a fragmented riverscape: A mitonuclear perspective

Abstract Aquatic invasive species are a significant threat to global freshwater biodiversity. This study focuses on the banded mystery snail, Callinina georgiana, an invasive species in the Adirondack region of northern New York—an important section of the New York Great Lakes Basin. This project aims to explore the genetic connectivity of C. georgiana within its invasive range using a combination of mitochondrial and nuclear markers. Sampling was conducted in the Raquette River and adjacent waterways, with a total of 229 snails collected from 16 distinct populations distributed across eight different waterbodies. Also included were two populations from the species' native range in the southern U.S.A. DNA was extracted, and a 710‐bp fragment of the mitochondrial DNA marker cytochrome c oxidase 1 and a 351‐bp fragment of nuclear marker histone‐3 were amplified. Population genetic analyses including haplotype patterning, AMOVA and genetic diversity estimates, neutrality tests and tests for isolation by distance were performed to assess connectivity patterns. Results showed moderate to high levels of genetic admixture within the snail's invasive range as indicated by the lack of geographic patterning of haplotypes and low to moderate levels of genetic differentiation across multiple sites. Demographic analyses combined with high numbers of private haplotypes indicate historic population expansion. Interestingly, a case of mitonuclear discordance was detected for native and invasive populations as evident by incongruent haplotype patterns for the cytochrome c oxidase 1 and histone‐3 markers. Callinina georgiana exhibits a high level of genetic connectivity in its invasive range. The presence of dams does not significantly affect apparent gene flow, indicating that anthropogenic activities, such as boat traffic might be key in dispersing the snails across this fragmented freshwater system. This study offers new insights into the dispersal and genetic structure of an invasive freshwater snail. It highlights the importance of considering anthropogenic factors when confronting complex patterns of genetic diversity. The findings are significant for biodiversity conservation and provide a basis for developing strategies to manage and contain the spread of aquatic invasive species such as C. georgiana, especially in regions with high human activity.

Clinging on the brink: Whole genomes reveal human-induced population declines and severe inbreeding in the Critically Endangered Emirati Leaf-toed Gecko (Asaccus caudivolvulus).

Human-mediated habitat destruction has had a profound impact on increased species extinction rates and population declines worldwide. The coastal development in the United Arab Emirates (UAE) over the last two decades, serves as an example of how habitat transformation can alter the landscape of a country in just a few years. Here, we study the genomic implications of habitat transformation in the Critically Endangered Emirati Leaf-toed Gecko (Asaccus caudivolvulus), the only endemic vertebrate of the UAE. We generate a high-quality reference genome for this gecko, representing the first reference genome for the family Phyllodactylidae, and produce whole-genome resequencing data for 23 specimens from 10 different species of leaf-toed geckos. Our results show that A. caudivolvulus has consistently lower genetic diversity than any other Arabian species of Asaccus, suggesting a history of ancient population declines. However, high levels of recent inbreeding are recorded among populations in heavily developed areas, with a more than 50% increase in long runs of homozygosity within a 9-year period. Moreover, results suggest that this species does not effectively purge deleterious mutations, hence making it more vulnerable to future stochastic threats. Overall, results show that A. caudivolvulus is in urgent need of protection, and habitat preservation must be warranted to ensure the species' survival.

Genetic diversity of North African populations in the 17q21 genomic region.

The demographic history of human populations in North Africa has been characterized by complex migration processes that have determined the current genetic structure of these populations. We examined the autosomal markers of eight sampled populations in northern Africa (Tunisia and Libya) to explore their genetic structure and to place them in a global context. We genotyped a set of 30 autosomal single-nucleotide polymorphisms (SNPs) extending 9.5Mb and encompassing the 17q21 inversion region. Our data include 403 individuals from Tunisia and Libya. To put our populations in the global context, we analyzed our data in comparison with other populations, including those of the 1000 Genomes Project. To evaluate the data, we conducted genetic diversity, principal component, STRUCTURE, and haplotype analyses. The analysis of genetic composition revealed the genetic heterogeneity of North African populations. The principal component and STRUCTURE analyses converged and revealed the intermediate position of North Africans between Europeans and Asians. Haplotypic analysis demonstrated that the normal (H1) and inverted (H2) polymorphisms in the chromosome 17q21 region occur in North Africa at frequencies similar to those found in European and Southwest Asian populations. The results highlight the complex demographic history of North Africa, reflecting the influence of genetic flow from Europe and the Near East that dates to the prehistoric period. These gene flows added to demographic factors (inbreeding, endogamy), natural factors (topography, Sahara), and cultural factors that play a role in the emergence of the diverse and heterogeneous genetic structures of North African populations. This study contributes to a better understanding of the complex structure of North African populations.

Potential domino effect of the 2023 Kahramanmaraş earthquake on the centuries-long seismic quiescence of the Dead Sea fault: inferences from the North Anatolian fault

Field observations conducted immediately following the February 6, 2023, Mw 7.8 Kahramanmaraş earthquake documented the southern surface rupture termination in the Amik Basin. The termination occurred in an en-echelon pattern, extending across the 3.5 km width of the approximately 10-km-wide stepover. This extension reached towards the northern tip of the Hacıpaşa Fault, which constitutes the main northern segment of the Dead Sea Fault Zone (DSFZ). Archaeoseismologic and paleoseismologic data show that the approximately 800-km-long DSFZ has been seismically quiet for more than 600 years in the north and 900 years in the south. A similar fault connection geometry at the western end of the 1939 Ms 7.9 Erzincan earthquake in the easternmost part of the North Anatolian Fault Zone and the subsequently triggered successive large magnitude earthquakes migrating westward within a few decades highlights an increased seismic hazard for the entire DSFZ. This heightened seismic hazard potential along the DSFZ, combined with historical population centers experiencing wars and migrations, puts millions of people at an unparalleled risk.

Using Runs of Homozygosity and Machine Learning to Disentangle Sources of Inbreeding and Infer Self-Fertilization Rates.

Runs of homozygosity (ROHs) are indicative of elevated homozygosity and inbreeding due to mating of closely related individuals. Self-fertilization can be a major source of inbreeding which elevates genome-wide homozygosity and thus should also create long ROHs. While ROHs are frequently used to understand inbreeding in the context of conservation and selective breeding, as well as for consanguinity of populations and their demographic history, it remains unclear how ROH characteristics are altered by selfing and if this confounds expected signatures of inbreeding due to demographic change. Using simulations, we study the impact of the mode of reproduction and demographic history on ROHs. We apply random forests to identify unique characteristics of ROHs, indicative of different sources of inbreeding. We pinpoint distinct features of ROHs that can be used to better characterize the type of inbreeding the population was subjected to and to predict outcrossing rates and complex demographic histories. Using additional simulations and four empirical datasets, two from highly selfing species and two from mixed-maters, we predict the selfing rate and validate our estimations. We find that self-fertilization rates are successfully identified even with complex demography. Population genetic summary statistics improve algorithm accuracy particularly in the presence of additional inbreeding, e.g. from population bottlenecks. Our findings highlight the importance of ROHs in disentangling confounding factors related to various sources of inbreeding and demonstrate situations where such sources cannot be differentiated. Additionally, our random forest models provide a novel tool to the community for inferring selfing rates using genomic data.

Biases in ARG-Based Inference of Historical Population Size in Populations Experiencing Selection.

Inferring the demographic history of populations provides fundamental insights into species dynamics and is essential for developing a null model to accurately study selective processes. However, background selection and selective sweeps can produce genomic signatures at linked sites that mimic or mask signals associated with historical population size change. While the theoretical biases introduced by the linked effects of selection have been well established, it is unclear whether ancestral recombination graph (ARG)-based approaches to demographic inference in typical empirical analyses are susceptible to misinference due to these effects. To address this, we developed highly realistic forward simulations of human and Drosophila melanogaster populations, including empirically estimated variability of gene density, mutation rates, recombination rates, purifying, and positive selection, across different historical demographic scenarios, to broadly assess the impact of selection on demographic inference using a genealogy-based approach. Our results indicate that the linked effects of selection minimally impact demographic inference for human populations, although it could cause misinference in populations with similar genome architecture and population parameters experiencing more frequent recurrent sweeps. We found that accurate demographic inference of D. melanogaster populations by ARG-based methods is compromised by the presence of pervasive background selection alone, leading to spurious inferences of recent population expansion, which may be further worsened by recurrent sweeps, depending on the proportion and strength of beneficial mutations. Caution and additional testing with species-specific simulations are needed when inferring population history with non-human populations using ARG-based approaches to avoid misinference due to the linked effects of selection.

Death on the permafrost: Revisiting the 1918-20 influenza pandemic in Alaska using death certificates.

The 1918-20 influenza pandemic devastated Alaska's Indigenous populations. We report on quantitative analyses of pandemic deaths due to pneumonia and influenza (P&I) using information from Alaska death certificates dating between 1915 and 1921 (n=7,147). Goals include a reassessment of pandemic death numbers, analysis of P&I deaths beyond 1919, estimates of excess mortality patterns overall and by age using intercensal population estimates based on Alaska's demographic history, and comparisons between Alaska Native (AN) and non-AN residents. Results indicate that ANs experienced 83% of all P&I deaths and 87% of all-cause excess deaths during the pandemic. AN mortality was 8.1 times higher than non-AN mortality. Analyses also uncovered previously unknown mortality peaks in 1920. Both subpopulations showed characteristically high mortality of young adults, possibly due to imprinting with the 1889-90 pandemic virus, but their age-specific mortality patterns were different: non-AN mortality declined after age 25-29 and stayed relatively low for the elderly, while AN mortality increased after age 25-29, peaked at age 40-44, and remained high up to age 64. This suggests a relative lack of exposure to H1-type viruses pre-1889 among AN persons. In contrast, non-AN persons, often temporary residents, may have gained immunity before moving to Alaska.

Objective Assessments of Smoking and Drinking Outperform Clinical Phenotypes in Predicting Variance in Epigenetic Aging

The reliability of the associations of the acceleration of epigenetic aging (EA) indices with clinical phenotypes other than for smoking and drinking is poorly understood. Furthermore, the majority of clinical phenotyping studies have been conducted using data from subjects of European ancestry. In order to address these limitations, we conducted clinical, physiologic, and epigenetic assessments of a cohort of 278 middle-aged African American adults and analyzed the associations with the recently described principal-components-trained version of GrimAge (i.e., PC-GrimAge) and with the DunedinPACE (PACE) index using regression analyses. We found that 74% of PC-GrimAge accelerated aging could be predicted by a simple baseline model consisting of age, sex, and methylation-sensitive digital PCR (MSdPCR) assessments of smoking and drinking. The addition of other serological, demographic, and medical history variables or PACE values did not meaningfully improve the prediction, although some variables did significantly improve the model fit. In contrast, clinical variables mapping to cardiometabolic syndrome did independently contribute to the prediction of PACE values beyond the baseline model. The PACE values were poorly correlated with the GrimAge values (r = 0.2), with little overlap in variance explained other than that conveyed by smoking and drinking. The results suggest that EA indices may differ in the clinical information that they provide and may have significant limitations as screening tools to guide patient care.