Medicine and Health Sciences Commons^™

Factors Associated With Blood Mercury Concentrations And Their Interactions With Three Glutathione S-Transferase Genes (Gstt1, Gstm1, And Gstp1): An Exposure Assessment Study Of Typically Developing Jamaican Children, Sheikh Farzana Zaman, Maureen Samms-Vaughan, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare Pellington, Katherine A Loveland, Mohammad H Rahbar

Journal Articles

BACKGROUND: Jamaican soil is abundant in heavy metals including mercury (Hg). Due to availability and ease of access, fish is a traditional dietary component in Jamaica and a significant source of Hg exposure. Mercury is a xenobiotic and known neuro-toxicant that affects children's neurodevelopment. Human glutathione S-transferase (GST) genes, including GSTT1, GSTM1, and GSTP1, affect Hg conjugation and elimination mechanisms.

METHODS: In this exposure assessment study we used data from 375 typically developing (TD) 2-8-year-old Jamaican children to explore the association between environmental Hg exposure, GST genes, and their interaction effects on blood Hg concentrations (BHgCs). We used multivariable general …

Factors Associated With Blood Mercury Concentrations And Their Interactions With Three Glutathione S-Transferase Genes (Gstt1, Gstm1, And Gstp1): An Exposure Assessment Study Of Typically Developing Jamaican Children, Sheikh Farzana Zaman, Maureen Samms-Vaughan, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare Pellington, Katherine A Loveland, Mohammad H Rahbar

Journal Articles

BACKGROUND: Jamaican soil is abundant in heavy metals including mercury (Hg). Due to availability and ease of access, fish is a traditional dietary component in Jamaica and a significant source of Hg exposure. Mercury is a xenobiotic and known neuro-toxicant that affects children's neurodevelopment. Human glutathione S-transferase (GST) genes, including GSTT1, GSTM1, and GSTP1, affect Hg conjugation and elimination mechanisms.

METHODS: In this exposure assessment study we used data from 375 typically developing (TD) 2-8-year-old Jamaican children to explore the association between environmental Hg exposure, GST genes, and their interaction effects on blood Hg concentrations (BHgCs). We used multivariable general …

Multi-Tissue Epigenetic Analysis Identifies Distinct Associations Underlying Insulin Resistance And Alzheimer's Disease At Cpt1a Locus, Chloé Sarnowski, Tianxiao Huan, Yiyi Ma, Roby Joehanes, Alexa Beiser, Charles S Decarli, Nancy L Heard-Costa, Daniel Levy, Honghuang Lin, Ching-Ti Liu, Chunyu Liu, James B Meigs, Claudia L Satizabal, Jose C Florez, Marie-France Hivert, Josée Dupuis, Philip L De Jager, David A Bennett, Sudha Seshadri, Alanna C Morrison

Journal Articles

BACKGROUND: Insulin resistance (IR) is a major risk factor for Alzheimer's disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus improving our understanding of the biological and regulatory mechanisms linking IR and AD.

METHODS: We conducted an epigenome-wide association study of IR, quantified using the homeostatic model assessment of IR (HOMA-IR) and adjusted for body mass index, in 3,167 participants from the Framingham Heart Study (FHS) without type 2 diabetes at the time of blood draw used for methylation measurement. We identified …

Systemic Interindividual Epigenetic Variation In Humans Is Associated With Transposable Elements And Under Strong Genetic Control, Chathura J Gunasekara, Harry Mackay, C Anthony Scott, Shaobo Li, Eleonora Laritsky, Maria S Baker, Sandra L Grimm, Goo Jun, Yumei Li, Rui Chen, Joseph L Wiemels, Cristian Coarfa, Robert A Waterland

Journal Articles

BACKGROUND: Genetic variants can modulate phenotypic outcomes via epigenetic intermediates, for example at methylation quantitative trait loci (mQTL). We present the first large-scale assessment of mQTL at human genomic regions selected for interindividual variation in CpG methylation, which we call correlated regions of systemic interindividual variation (CoRSIVs). These can be assayed in blood DNA and do not reflect interindividual variation in cellular composition.

RESULTS: We use target-capture bisulfite sequencing to assess DNA methylation at 4086 CoRSIVs in multiple tissues from each of 188 donors in the NIH Gene-Tissue Expression (GTEx) program. At CoRSIVs, DNA methylation in peripheral blood correlates with …

Integrative Analysis Of Clinical And Epigenetic Biomarkers Of Mortality, Tianxiao Huan, Steve Nguyen, Elena Colicino, Carolina Ochoa-Rosales, W David Hill, Jennifer A Brody, Mette Soerensen, Yan Zhang, Antoine Baldassari, Mohamed Ahmed Elhadad, Tanaka Toshiko, Yinan Zheng, Arce Domingo-Relloso, Dong Heon Lee, Jiantao Ma, Chen Yao, Chunyu Liu, Shih-Jen Hwang, Roby Joehanes, Myriam Fornage, Jan Bressler, Joyce B J Van Meurs, Birgit Debrabant, Jonas Mengel-From, Jacob Hjelmborg, Kaare Christensen, Pantel Vokonas, Joel Schwartz, Sina A Gahrib, Nona Sotoodehnia, Colleen M Sitlani, Sonja Kunze, Christian Gieger, Annette Peters, Melanie Waldenberger, Ian J Deary, Luigi Ferrucci, Yishu Qu, Philip Greenland, Donald M Lloyd-Jones, Lifang Hou, Stefania Bandinelli, Trudy Voortman, Brenner Hermann, Andrea Baccarelli, Eric Whitsel, James S Pankow, Daniel Levy

Journal Articles

DNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p < 1 × 10

Elucidating Mechanisms Of Genetic Cross-Disease Associations At The Procr Vascular Disease Locus, David Stacey, Lingyan Chen, Paulina J Stanczyk, Joanna M M Howson, Amy M Mason, Stephen Burgess, Stephen Macdonald, Jonathan Langdown, Harriett Mckinney, Kate Downes, Neda Farahi, James E Peters, Saonli Basu, James S Pankow, Weihong Tang, Nathan Pankratz, Maria Sabater-Lleal, Paul S De Vries, Nicholas L Smith, Amy D Gelinas, Daniel J Schneider, Nebojsa Janjic, Nilesh J Samani, Shu Ye, Charlotte Summers, Edwin R Chilvers, John Danesh, Dirk S Paul

Journal Articles

Many individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk. We identify PROCR-p.Ser219Gly as the likely causal variant at the locus and protein C as a causal factor. Using genetic analyses, human recall-by-genotype and in vitro experimentation, we demonstrate that PROCR-219Gly increases plasma levels of (activated) protein C through endothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, …

Additive And Interactive Associations Of Environmental And Sociodemographic Factors With The Genotypes Of Three Glutathione S-Transferase Genes In Relation To The Blood Arsenic Concentrations Of Children In Jamaica, Mohammad H Rahbar, Maureen Samms-Vaughan, Yuansong Zhao, Sepideh Saroukhani, Sheikh F Zaman, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakspeare-Pellington, Katherine A Loveland

Journal Articles

Arsenic (As) is a metalloid that has been classified as a xenobiotic with toxic effects on human beings, especially on children. Since the soil in Jamaica contains As, dietary intake is considered the main source of As exposure in Jamaicans. In addition, glutathione S-transferase (GST) genes, including

The Impact Of The Th17:Treg Axis On The Iga-Biome Across The Glycemic Spectrum, Heather T Essigmann, Kristi L Hoffman, Joseph F Petrosino, Goo Jun, David Aguilar, Craig L Hanis, Herbert L Dupont, Eric L Brown

Journal Articles

Secretory IgA (SIgA) is released into mucosal surfaces where its function extends beyond that of host defense to include the shaping of resident microbial communities by mediating exclusion/inclusion of respective microbes and regulating bacterial gene expression. In this capacity, SIgA acts as the fulcrum on which host immunity and the health of the microbiota are balanced. We recently completed an analysis of the gut and salivary IgA-Biomes (16S rDNA sequencing of SIgA-coated/uncoated bacteria) in Mexican-American adults that identified IgA-Biome differences across the glycemic spectrum. As Th17:Treg ratio imbalances are associated with gut microbiome dysbiosis and chronic inflammatory conditions such as …

Highly Variable Recessive Lthal Or Nearly Lethal Mutation Rates During Germ-Line Development Of Male Drosophila Melanogaster, Jian-Jun Gao, Xue-Rong Pan, Jing Hu, Li Ma, Jian-Min Wu, Ye-Lin Shao, Sara A Barton, Ronny C Woodruff, Ya-Ping Zhang, Yun-Xin Fu

Journal Articles

Each cell of higher organism adults is derived from a fertilized egg through a series of divisions, during which mutations can occur. Both the rate and timing of mutations can have profound impacts on both the individual and the population, because mutations that occur at early cell divisions will affect more tissues and are more likely to be transferred to the next generation. Using large-scale multigeneration screening experiments for recessive lethal or nearly lethal mutations of Drosophila melanogaster and recently developed statistical analysis, we show for male D. melanogaster that (i) mutation rates (for recessive lethal or nearly lethal) are …