Biology subjects

Oh, S. S.

Publications and source records attributed to Oh, S. S..

9 recordsLinked to original sources

bioRxiv2026

A chorionic gonadotropin assay enables non-invasive detection of ovulation and early pregnancy in a New World primate model

Early detection of ovulation and pregnancy in the common marmoset is crucial for reproductive studies, yet hCG kits lack cross-reactivity with marmoset CG, and current methods remain labor-intensive. Here, we developed monoclonal antibodies against marmoset CG and CG{beta}, and established a non-invasive immunochromatographic CG assay. By eliminating invasive blood sampling, this assay supports 3Rs principles and enables practical endocrine monitoring. The assay detected urinary CG surges preceding ovulation, enabling efficient embryo recovery through artificial insemination (75%). Early pregnancy was detected at approximately 17 days post-ovulation. In addition, pregnancy detection in squirrel monkeys suggests conservation of CG features among certain New World primates. Overall, this simple, non-invasive assay provides a practical tool for marmoset research and establishes a foundation for future conservation-oriented reproductive monitoring following appropriate species-specific validation.

physiology↗

bioRxiv2021

Gene expression in African Americans and Latinos reveals ancestry-specific patterns of genetic architecture

We analyzed whole genome and RNA sequencing data from 2,733 African American and Hispanic/Latino children to explore ancestry- and heterozygosity-related differences in the genetic architecture of whole blood gene expression. We found that heritability of gene expression significantly increases with greater proportion of African genetic ancestry and decreases with higher levels of Indigenous American ancestry, consistent with a relationship between heterozygosity and genetic variance. Among heritable protein-coding genes, the prevalence of statistically significant ancestry-specific expression quantitative trait loci (anc-eQTLs) was 30% in African ancestry and 8% for Indigenous American ancestry segments. Most of the anc-eQTLs (89%) were driven by population differences in allele frequency, demonstrating the importance of measuring gene expression across multiple populations. Transcriptome-wide association analyses of multi-ancestry summary statistics for 28 traits identified 79% more gene-trait pairs using models trained in our admixed population than models trained in GTEx. Our study highlights the importance of large and ancestrally diverse genomic studies for enabling new discoveries of complex trait architecture and reducing disparities.

genetics↗

bioRxiv2020

Integrative genomic analysis in African American children with asthma finds 3 novel loci associated with lung function

Bronchodilator drugs are commonly prescribed for treatment and management of obstructive lung function present with diseases such as asthma. Administration of bronchodilator medication can partially or fully restore lung function as measured by pulmonary function tests. The genetics of baseline lung function measures taken prior to bronchodilator medication has been extensively studied, and the genetics of the bronchodilator response itself has received some attention. However, few studies have focused on the genetics of post-bronchodilator lung function. To address this gap, we analyzed lung function phenotypes in 1,103 subjects from the Study of African Americans, Asthma, Genes, and Environment (SAGE), a pediatric asthma case-control cohort, using an integrative genomic analysis approach that combined genotype, locus-specific genetic ancestry, and functional annotation information. We integrated genome-wide association study (GWAS) results with an admixture mapping scan of three pulmonary function tests (FEV1, FVC, and FEV1/FVC) taken before and after albuterol bronchodilator administration on the same subjects, yielding six traits. We identified 18 GWAS loci, and 5 additional loci from admixture mapping, spanning several known and novel lung function candidate genes. Most loci identified via admixture mapping exhibited wide variation in minor allele frequency across genotyped global populations. Functional fine-mapping revealed an enrichment of epigenetic annotations from peripheral blood mononuclear cells, fetal lung tissue, and lung fibroblasts. Our results point to three novel potential genetic drivers of pre- and post-bronchodilator lung function: ADAMTS1, RAD54B, and EGLN3.

genetics↗

bioRxiv2019

A Dual-sensing DNA Nanostructure with an Ultra-broad Detection Range

Despite considerable interest in the development of biosensors that can measure analyte concentrations with a dynamic range spanning many orders of magnitude, this goal has proven difficult to achieve. We describe here a modular biosensor architecture that integrates two different readout mechanisms into a single-molecule construct that can achieve target detection across an extraordinarily broad dynamic range. Our dual-mode readout DNA biosensor (DMRD) combines an aptamer and a DNAzyme to quantify ATP with two different mechanisms, which respond to low (micromolar) and high (millimolar) concentrations by generating distinct readouts based on changes in fluorescence and absorbance, respectively. Importantly, we have also devised regulatory strategies to finely tune the target detection range of each sensor module by controlling the target-sensitivity of each readout mechanism. Using this strategy, we report the detection of ATP at a dynamic range spanning 1-500,000 M--more than five orders of magnitude, representing the largest dynamic range reported to date with a single biosensor construct.

bioengineering↗

bioRxiv2019

On the cross-population portability of gene expression prediction models

The genetic control of gene expression is a core component of human physiology. For the past several years, transcriptome-wide association studies have leveraged large datasets of linked genotype and RNA sequencing information to create a powerful gene-based test of association that has been used in dozens of studies. While numerous discoveries have been made, the populations in the training data are overwhelmingly of European descent, and little is known about the generalizability of these models to other populations. Here, we test for cross-population generalizability of gene expression prediction models using a dataset of African American individuals with RNA-Seq data in whole blood. We find that the default models trained in large datasets such as GTEx and DGN fare poorly in African Americans, with a notable reduction in prediction accuracy when compared to European Americans. We replicate these limitations in cross-population generalizability using the five populations in the GEUVADIS dataset. Via realistic simulations of both populations and gene expression, we show that accurate cross-population generalizability of transcriptome prediction only arises when eQTL architecture is substantially shared across populations. In contrast, models with non-identical eQTLs showed patterns similar to real-world data. Therefore, generating RNA-Seq data in diverse populations is a critical step towards multi-ethnic utility of gene expression prediction. Author summaryAdvances in RNA sequencing technology have reduced the cost of measuring gene expression at a genome-wide level. However, sequencing enough human RNA samples for adequately-powered disease association studies remains prohibitively costly. To this end, modern transcriptome-wide association analysis tools leverage existing paired genotype-expression datasets by creating models to predict gene expression using genotypes. These predictive models enable researchers to perform cost-effective association tests with gene expression in independently genotyped samples. However, most of these models use European reference data, and the extent to which gene expression prediction models work across populations is not fully resolved. We observe that these models predict gene expression worse than expected in a dataset of African-Americans when derived from European-descent individuals. Using simulations, we show that gene expression predictive model performance depends on both the amount of shared genotype predictors as well as the genetic relatedness between populations. Our findings suggest a need to carefully select reference populations for prediction and point to a pressing need for more genetically diverse genotype-expression datasets.

genomics↗

bioRxiv2018

Drinking motives and alcohol use among college students with the alcohol flush reaction: A nationwide study

BackgroundThis study investigated the relationship between drinking motives and alcohol use among a nationally representative sample of college students with the alcohol flush reaction (AFR). We surveyed and analyzed the data of 2,245 male and 2,326 female college students in a nationally representative sample of 82 colleges in South Korea.\n\nMethodsOf our study population, 725 males (32.3%) and 812 females (34.9%) reported to currently suffering from AFR. Multiple regression analysis was used to identify the association between drinking motives and drinking behavior, measured via the AUDIT.\n\nResultsRelative to drinking because of peer pressure, students drinking for pleasure (males: {beta} = 2.622, p <.0001; females {beta} = 2.769, p <.0001) or stress/depression (males: {beta} = 2.479, p <.0001; females {beta} = 2.489, p <.0001) had higher AUDIT scores. Among students drinking because of stress/depression, seniors (males: {beta} = 3.603, p<.0001; females: {beta} = 3.791, p = 0.000), smokers (males: {beta} = 1.564, p = 0.000; females {beta} = 1.816, p = 0.007) and/or liberal arts students (males: {beta} = 6.1136, p<.0001; females {beta} = 4.2105, p <.0001) consumed more alcohol than their peers. Relative to conformity motives, enhancement and coping motives were found to have a greater influence on alcohol intake among college students with alcohol flush reaction.\n\nConclusionConsidering that the flush reaction can occur in AFR individuals after just one sip of wine, our results show that educators and policymakers must take action to deal with this problem.

epidemiology↗

bioRxiv2018

Genetic Determinants of Telomere Length in African American Youth

Telomere length (TL) is associated with numerous disease states and is affected by genetic and environmental factors. However, TL has been mostly studied in adult populations of European or Asian ancestry. These studies have identified 34 TL-associated genetic variants recently used as genetic proxies for TL. The generalizability of these associations to pediatric populations and racially diverse populations, specifically of African ancestry, remains unclear. Furthermore, six novel variants associated with TL in a population of European children have been identified but not validated. We measured TL from whole blood samples of 492 healthy African American youth (children and adolescents between 8 and 20 years old) and performed the first genome-wide association study of TL in this population. We were unable to replicate neither the 34 reported genetic associations found in adults nor the six genetic associations found in European children. However, we discovered a novel genome-wide significant association between TL and rs1483898 on chromosome 14. Our results underscore the importance of examining these genetic associations with TL in diverse pediatric populations such as African Americans.

genetics↗

bioRxiv2017

A Genome-wide Association and Admixture Mapping Study of Bronchodilator Drug Response in African Americans with Asthma

BackgroundShort-acting B2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the U.S 1, 2. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma3\n\nObjectiveTo identify genetic variants that may contribute to differences in BDR in African Americans with asthma.\n\nMethodsWe performed a genome-wide association study of BDR in 949 African American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase 3 genotypes. We used linear regression models adjusting for age, sex, body mass index and genetic ancestry to test for an association between BDR and genotype at single nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1,830 Latinos (Total=2,779). Lastly, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. Two additional populations of 416 Latinos and 1,325 African Americans were used to replicate significant associations.\n\nResultsWe identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p=7.69 x 10-9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958, and rs7081864, p[≤]5 x 10-8).\n\nConclusionsOur findings indicate that both population specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.\n\nKey messagesO_LIA GWAS for BDR in African American children with asthma identified an intergenic population specific variant at 9q21 to be associated with increased bronchodilator drug response (BDR).\nC_LIO_LIA meta-analysis of GWAS across African Americans and Latinos identified shared genetic variants at 10q21 in the intron of PRKG1 to be associated with differences in BDR.\nC_LIO_LIFurther genetic studies need to be performed in diverse populations to identify the full set of genetic variants that contribute to BDR.\nC_LI

genomics↗

bioRxiv2017

Whole Genome Sequencing of Pharmacogenetic Drug Response in Racially and Ethnically Diverse Children with Asthma

Asthma is the most common chronic disease of children, with significant racial/ethnic differences in prevalence, morbidity, mortality and therapeutic response. Albuterol, a bronchodilator medication, is the first-line therapy for asthma treatment worldwide. We performed the largest whole genome sequencing (WGS) pharmacogenetics study to date using data from 1,441 minority children with asthma who had extremely high or low bronchodilator drug response (BDR). We identified population-specific and shared pharmacogenetic variants associated with BDR, including genome-wide significant (p < 3.53 x 10-7) and suggestive (p < 7.06 x 10-6) loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and {beta}-adrenergic signaling pathways (ADAMTS3 and COX18). Functional analyses centered on NFKB1 revealed potential regulatory function of our BDR-associated SNPs in bronchial smooth muscle cells. Specifically, these variants are in linkage disequilibrium with SNPs in a functionally active enhancer, and are also expression quantitative trait loci (eQTL) for a neighboring gene, SLC39A8. Given the lack of other asthma study populations with WGS data on minority children, replication of our rare variant associations is infeasible. We attempted to replicate our common variant findings in five independent studies with GWAS data. The age-specific associations previously found in asthma and asthma-related traits suggest that the over-representation of adults in our replication populations may have contributed to our lack of statistical replication, despite the functional relevance of the NFKB1 variants demonstrated by our functional assays. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations.\n\nAUTHOR SUMMARYAsthma is the most common chronic disease among children. Albuterol, a bronchodilator medication, is the first-line therapy for asthma treatment worldwide. In the U.S., asthma prevalence is the highest among Puerto Ricans, intermediate among African Americans and lowest in Whites and Mexicans. Asthma disparities extend to mortality, which is four- to five-fold higher in Puerto Ricans and African Americans compared to Mexicans [1]. Puerto Ricans and African Americans, the populations with the highest asthma prevalence and death rate, also have the lowest albuterol bronchodilator drug response (BDR). We conducted the largest pharmacogenetic study using whole genome sequencing data from 1,441 minority children with asthma who had extremely high or low albuterol bronchodilator drug response. We identified population-specific and shared pharmacogenetic variants associated with BDR. Our findings help inform the direction of future development of asthma medications and our study advances the foundation of precision medicine for at-risk, yet understudied, racially/ethnically diverse populations.

genetics↗