Biomedical subjects

Kelly M Bakulski

Publications and source records attributed to Kelly M Bakulski.

3 recordsLinked to original sources

PubMed2026

MethylModes: computationally efficient detection of multimodal distributions in DNA methylation data.

SUMMARY: MethylModes is an R package and Shiny application to identify multimodal distributions in human DNA methylation at individual CpG sites. Multimodal distributions, which can be the result of nearby genetic variation, environmental exposures, or assay artifacts, are susceptible to confounding and important to identify for methylation analysis. MethylModes is easily incorporated into existing quality control pipelines of array-based DNA methylation data. The underlying algorithm uses kernel smoothing of probe-level data to locate the number and location of peaks. The algorithm can be parallelized across probes for efficient implementation at genome-scale. We provide a case study implementation of MethylModes in the Health and Retirement Study as well as the Airwave Health Monitoring Study. AVAILABILITY AND IMPLEMENTATION: MethylModes is available on GitHub at https://github.com/lutiffan/methylModes as an R package wrapping an R Shiny application. We include a toy dataset to validate installation. The codebase is also published on Zenodo at https://doi.org/10.5281/zenodo.17448517.

DNA Methylation↗

PubMed2025

Perinatal Lead (Pb) Exposure Increases Mouse Embryonic Weight and Alters Neuronal Gene Expression.

Acute and chronic exposure to lead (Pb) during pregnancy is linked to adverse health outcomes, including delayed neurodevelopment in offspring. However, the pathways by which Pb exposure influences long-term health remain poorly understood. To address this, we measured the effects of perinatal Pb exposure on gene expression including imprinted genes, X-linked genes, and sexually dimorphic genes. Female mice were given control or Pb acetate dosed (32 ppm) drinking water two weeks prior to timed mating until embryonic day (E)10-12, upon which whole embryos were collected, weighed, and sexed at E13-15. From a subset of embryo heads (n≥9 per sex per group), we extracted and sequenced RNA. We used linear regression to assess Pb impacts on embryonic weight and gene expression across all mice and stratified by sex. Among the differentially expressed genes, we identified significantly enriched pathways. Pb-exposed embryos weighed more than controls (p=0.007), across both sexes. Collectively, we identified 2,920 differentially expressed genes (FDR<0.05), including 31 imprinted genes and 120 X-linked genes upon Pb exposure. Pb exposure altered expression in gene pathways related to neuronal structure and function as well as sexually dimorphic genes (44 for females; 76 for males). These findings highlight perinatal Pb-linked alterations that may drive later-life health outcomes.

DOHaD↗

PubMed2025

DNA methylation age deviation and cognitive status among older adults in the US, NHANES 1999-2002.

Biological aging, measured using DNA methylation, is a potential biomarker for cognitive health outcomes. We evaluated associations between DNA methylation measures of aging and cognition in a nationally representative sample of adults aged 60+ in the National Health and Nutrition Examination Survey (NHANES), 1999-2002. Genome-wide DNA methylation data were used to create 13 measures of biological aging trained on different aging phenotypes. Cognition was assessed with the Digit Symbol Substitution Test (DSST). To evaluate associations between each DNA methylation measure and DSST score, survey-weighted linear regression models adjusted for age, sex, race/ethnicity, education, smoking, serum cotinine, and BMI were run. We assessed effect modification by sex, education, and race and ethnicity. Included participants (N=1,463) were an average of 70.5 years old and 82.7% non-Hispanic White. The average DSST score was 46.9 (SD 17.6). Ten of 13 DNA methylation measures were associated with DSST (adjusted p<0.05). One year of GrimAge2 accelerated aging was associated with -0.41 points lower DSST score (95% CI: -0.61, -0.21; adjusted p=5×10-4). In stratified analyses, higher magnitudes of association were observed among male and non-Hispanic White participants across multiple aging measures. DNA methylation may be a useful biomarker of cognitive status among older adults.

DNA methylation↗