Leveraging human genetic and adverse outcome pathway (AOP) data to inform susceptibility in human health risk assessment.

Mammalian Genome : Official Journal of the International Mammalian Genome Society
Holly M MortensenSusan Y Euling

Abstract

Estimation of susceptibility differences in human health risk assessment (HHRA) has been challenged by a lack of available susceptibility and variability data after exposure to a specific environmental chemical or pharmaceutical. With the increasingly large number of available data sources that contain polymorphism and other genetic data, human genetic variability that informs susceptibility can be better incorporated into HHRA. A recent policy, the 2016 The Frank R. Lautenberg Chemical Safety for the twenty-first Century Act, requires the US Environmental Protection Agency to evaluate new and existing toxic chemicals with explicit consideration of susceptible populations of all types (life stage, exposure, genetic, etc.). We propose using the adverse outcome pathway (AOP) construct to organize, identify, and characterize human genetic susceptibility in HHRA. We explore how publicly available human genetic datasets can be used to gain mechanistic understanding of molecular events and characterize human susceptibility for an adverse outcome. We present a computational method that implements publicly available human genetic data to prioritize AOPs with potential for human genetic variability. We describe the application of this a...Continue Reading

References

Oct 16, 1999·American Journal of Industrial Medicine·G JohansonF Bois
Aug 10, 2002·Bioinformatics·Trey IdekerAndrew F Siegel
Oct 14, 2003·Nature Biotechnology·Ziv Bar-JosephDavid K Gifford
Mar 3, 2004·Genome Research·Berend Snel, Martijn A Huynen
Oct 23, 2004·Science·UNKNOWN ENCODE Project Consortium
Oct 30, 2004·Nature Genetics·Gary A ChurchillUNKNOWN Complex Trait Consortium
Oct 29, 2005·Nature·UNKNOWN International HapMap Consortium
Jul 21, 2006·Nucleic Acids Research·Debraj GuhaThakurta
Jul 27, 2006·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S InoueA Rostami-Hodjegan
Aug 25, 2006·Clinical Pharmacokinetics·Trevor N JohnsonGeoffrey T Tucker
Sep 12, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·David J DixRobert J Kavlock
Nov 10, 2006·Biology of Reproduction·C Edwin GarnerB I Ghanayem
Jan 2, 2007·PLoS Computational Biology·Yuan Qi, Hui Ge
Feb 3, 2007·Nature Reviews. Drug Discovery·Amin Rostami-Hodjegan, Geoffrey T Tucker
Feb 15, 2007·British Journal of Clinical Pharmacology·Gemma L DickinsonAmin Rostami-Hodjegan
Oct 19, 2007·Nature·UNKNOWN International HapMap ConsortiumJohn Stewart
Feb 16, 2008·Science·Francis S CollinsJohn R Bucher
Aug 30, 2008·Genomics·Ali TorkamaniNicholas J Schork
Dec 17, 2008·Risk Analysis : an Official Publication of the Society for Risk Analysis·Robert J KavlockRaymond R Tice
Feb 10, 2009·Expert Opinion on Drug Metabolism & Toxicology·Masoud JameiAmin Rostami-Hodjegan
Apr 24, 2009·Journal of Biomolecular Structure & Dynamics·K Krishna KumarP N Suganthan
Jul 30, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Fang LiuGaku Ichihara
Sep 1, 2009·Methods in Molecular Biology·Wataru FujibuchiHideko Sone
Feb 9, 2010·Molecular Genetics and Metabolism·Stéphane CauchiPiero Marchetti
Feb 26, 2010·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Gary GinsbergBabasaheb Sonawane
Mar 17, 2010·Trends in Genetics : TIG·Norann A Zaghloul, Nicholas Katsanis
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jul 20, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Daniel M RotroffRussell S Thomas
Sep 8, 2010·Environmental Toxicology and Chemistry·Gerald T AnkleyDaniel L Villeneuve
Oct 22, 2010·Environmental Health Perspectives·Jason D SacksMary Ross
Oct 29, 2010·Nature·Gonçalo R AbecasisGil A McVean
Dec 8, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Blair U BradfordIvan Rusyn
Dec 18, 2010·Nature Reviews. Genetics·Albert-László BarabásiJoseph Loscalzo
Apr 14, 2011·European Journal of Human Genetics : EJHG·Brooke L Fridley, Joanna M Biernacka
Sep 29, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Barbara A WetmoreRussell S Thomas
Nov 15, 2011·Molecular BioSystems·Richard S JudsonFathi Elloumi

❮ Previous
Next ❯

Citations

May 31, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Allan Peter DavisCarolyn J Mattingly
Feb 21, 2018·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Ivan RusynKaren L Svenson
Jul 15, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Allan Peter DavisCarolyn J Mattingly
Dec 18, 2020·Risk Analysis : an Official Publication of the Society for Risk Analysis·Rogelio Tornero-VelezTimothy J Buckley
Mar 8, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Anke M TukkerKimberly A McAllister
Jul 14, 2021·Scientific Data·Holly M MortensenAntony J Williams

❮ Previous
Next ❯

Software Mentioned

Simcyp
High
AOPwiki
HHRA
GTex
- Throughput Toxicokinetic ( HTTK ) R - package
DisGeNET
Simcyp simulator
Ensembl Regulatory Build
Ensembl

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.