Biology subjects

Yee, M.-C.

Publications and source records attributed to Yee, M.-C..

4 recordsLinked to original sources

bioRxiv2019

Rapid response to the Alpha-1 Adrenergic Agent Phenylephrine in the Perioperative Period is Impacted by Genomics and Ancestry

BackgroundThe emergence of genomic data in biobanks and health systems offers new ways to derive medically important phenotypes, including acute phenotypes that occur during in-patient clinical care. We hypothesized that there is a genetic underpinning to the magnitude of the response to phenylephrine, an 1-adrenergic receptor agonist commonly used to treat hypotension during anesthesia and surgery.\n\nMethodsWe quantified the response to phenylephrine by determining the delta between the minimum blood pressure (BP) within five minutes before and the maximum BP within five minutes after bolus administration. We then performed a genome-wide association study (GWAS) adjusted for genetic ancestry, demographics, and relevant clinical covariates to investigate genetic factors underlying individual differences systolic BP response to phenylephrine ({Delta}SBP), as well as mean arterial pressure ({Delta}MAP) and diastolic BP ({Delta}DBP), for both the entire study cohort as well as for each of 3 ancestry sub-cohorts; European American(EA), African American(AA), and Hispanic American(HA).\n\nResults4,317 patients met inclusion criteria, of which 3,699 were genotyped. Average {Delta}BP values over the entire cohort were {Delta}SBP=17(+-25) mmHg, {Delta}MAP=14(+-18) mmHg, {Delta}DBP=11(+-14) mmHg. The largest difference between populations was observed for {Delta}SBP ({Delta}SBPEA=20(+-24) mmHg; {Delta}SBPHA=16(+-25) mmHg; {Delta}SBPAA=15(+-25) mmHg). The differences remained after adjusting for clinical covariates and ancestry (EA vs. HA: {Delta}SBP, p<0.032;{Delta}MAP, p<0.021;{Delta}DBP,p<0.008);(EA vs. AA:{Delta}SBP,p<5.13x10-5;{Delta}MAP,p<2.1x10-4;{Delta}DBP,p<3.3x10-4). GWAS revealed significant associations between loci and BP response in 5 different genome regions (p<5x10-8) in the entire cohort, and suggestive associations in 2 different regions in EAs (p<6x10-8,p<7x10-8). We observed non-random enrichment in association with SBP drug response in 165 loci previously reported to be associated with systolic blood pressure. Finally, we discovered rare variants, rs188427942 and rs147664194 present at [~]1% in EAs and rs146535276 present at [~]1% in AAs respectively, where patients carrying one copy of these variants show no response to phenylephrine.\n\nConclusionsIt is possible to derive a quantitative phenotype suited for comparative statistics and genome-wide association studies from routinely collected perioperative data. There are population differences in rapid response to phenylephrine, large effect alleles and novel genes affecting pharmaceutical response, and phenylephrine non-responders, with implications for personalized treatment during surgery.

genomics↗

bioRxiv2017

Genomic insights into the domestication of the chocolate tree, Theobroma cacao L.

Domestication has had a strong impact on the development of modern societies. We sequenced 200 genomes of the chocolate plant Theobroma cacao L. to show for the first time that a single population underwent strong domestication approximately 3,600 years (95% CI: 2481 - 10,903 years ago) ago, the Criollo population. We also show that during the process of domestication, there was strong selection for genes involved in the metabolism of the colored protectants anthocyanins and the stimulant theobromine, as well as disease resistance genes. Our analyses show that domesticated populations of T. cacao (Criollo) maintain a higher proportion of high frequency deleterious mutations. We also show for the first time the negative consequences the increase accumulation of deleterious mutations during domestication on the fitness of individuals (significant negative correlation between Criollo ancestry and Kg of beans per hectare per year, P = 0.000425).

genomics↗

bioRxiv2017

Genetic Identification Of A Common Collagen Disease In Puerto Ricans Via Identity-By-Descent Mapping In A Health System

Achieving confidence in the causality of a disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with genetic relatedness that also underlies extreme short stature. We link the gene, COL27A1, with a little-known genetic disease, previously thought to be rare and recessive. We demonstrate that disease manifests in both heterozygotes and homozygotes, indicating a common collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian disease.

genomics↗

bioRxiv2016

Time dependent genetic analysis links field and controlled environment phenotypes in the model C4 grass Setaria

Vertical growth of plants is a dynamic process that is influenced by genetic and environmental factors and has a pronounced effect on overall plant architecture and biomass composition. We have performed twelve controlled growth trials of an interspecific Setaria italica x Setaria viridis recombinant inbred line population to assess how the genetic architecture of plant height is influenced by developmental queues, water availability and planting density. The nondestructive nature of plant height measurements has enabled us to monitor vertical growth throughout the plant life cycle in both field and controlled environments. We find that plant height is reduced under water limitation and high density planting and affected by growth environment (field vs. growth chamber). The results support a model where plant height is a heritable, polygenic trait and that the major genetic loci that influence plant height function independent of growth environment. The identity and contribution of loci that influence height changes dynamically throughout development and the reduction of growth observed in water limited environments is a consequence of delayed progression through the genetic program which establishes plant height in Setaria. In this population, alleles inherited from the weedy S. viridis parent act to increase plant height early, whereas a larger number of small effect alleles inherited from the domesticated S. italica parent collectively act to increase plant height later in development.

plant biology↗