The Genetic Architecture of Arsenic Metabolism Efficiency:A SNP-Based Heritability Study of Bangladeshi Adults

Environmental Health Perspectives
Jianjun GaoBrandon L Pierce

Abstract

Consumption of arsenic-contaminated drinking water adversely affects health. There is interindividual variation in arsenic metabolism efficiency, partially due to genetic variation in the arsenic methyltransferase (AS3MT) gene region. The goal of this study was to assess the overall contribution of genetic factors to variation in arsenic metabolism efficiency, as measured by the relative concentration of dimethylarsinic acid (DMA%) in urine. Using data on genome-wide single nucleotide polymorphisms (SNPs) and urinary DMA% for 2,053 arsenic-exposed Bangladeshi individuals, we employed various SNP-based approaches for heritability estimation and polygenic modeling. Using data on all participants, the percent variance explained (PVE) for DMA% by all measured and imputed SNPs was 16% (p = 0.08), which was reduced to 5% (p = 0.34) after adjusting for AS3MT SNPs. Using information on close relatives only, the PVE was 63% (p = 0.0002), but decreased to 41% (p = 0.01) after adjusting for AS3MT SNPs. Regional heritability analysis confirmed 10q24.32 (AS3MT) as a major arsenic metabolism locus (PVE = 7%, p = 4.4 × 10(-10)), but revealed no additional regions. We observed a moderate association between a polygenic score reflecting elevate...Continue Reading

References

Sep 1, 1988·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·C J ChenH Y Wu
Jun 30, 1998·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·M S GolubN Baumrind
Jul 28, 2004·Toxicology and Applied Pharmacology·Takahiko YoshidaGui Fan Sun
Jul 28, 2004·Toxicology and Applied Pharmacology·David J ThomasMiroslav Styblo
Mar 4, 2005·Environmental Health Perspectives·Olga L ValenzuelaLuz M Del Razo
Sep 15, 2005·Journal of Exposure Science & Environmental Epidemiology·Habibul AhsanJoseph Graziano
Jun 30, 2006·Journal of Biomedical Science·Hsin-Su YuChee-Yin Chai
Dec 30, 2006·PLoS Genetics·Nick PattersonDavid Reich
Mar 17, 2007·Journal of Toxicology and Environmental Health. Part a·Craig SteinmausAllan H Smith
Jun 6, 2007·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Habibul AhsanJoseph H Graziano
Jul 20, 2007·Environmental Health Perspectives·Anna-Lena LindbergMarie Vahter
Nov 21, 2007·Human & Experimental Toxicology·A VahidniaF A de Wolff
Dec 7, 2007·Environmental Health : a Global Access Science Source·Carrie V BretonDavid C Christiani
May 31, 2008·Environmental Research·Ismail CelikAnthony J Alberg
Jun 21, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jie Liu, Michael P Waalkes
Jul 22, 2008·Mutation Research·Pritha GhoshKunal Ray
Sep 12, 2008·Regulatory Toxicology and Pharmacology : RTP·Pamela J MinkJoyce S Tsuji
Feb 5, 2009·Environmental Geochemistry and Health·Mohammad Mahmudur RahmanRavi Naidu
Jan 5, 2010·Environmental Research·Leiliane PaivaRicardo Marcos
Jun 22, 2010·Nature Genetics·Jian YangPeter M Visscher
Jul 31, 2010·Environmental Research·Kristin E PorterChristine F Skibola
Nov 9, 2010·Genetic Epidemiology·Yun LiGonçalo R Abecasis
Dec 21, 2010·American Journal of Human Genetics·Jian YangPeter M Visscher
Dec 24, 2010·American Journal of Epidemiology·Brandon L PierceHabibul Ahsan
Mar 8, 2011·American Journal of Epidemiology·Molly L KileDavid C Christiani
May 18, 2011·American Journal of Epidemiology·Maria ArgosHabibul Ahsan
Jul 7, 2011·International Journal of Molecular Sciences·Tetsuro AgusaHisato Iwata
Jul 22, 2011·International Journal of Environmental Research and Public Health·Jianwei GaoLinsheng Yang
Sep 15, 2011·The Kaohsiung Journal of Medical Sciences·Chun Fa HuangShing Hwa Liu
Dec 6, 2011·Environmental Health Perspectives·Lalita N AbhyankarAna Navas-Acien
Feb 22, 2012·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Ema G RodriguesDavid C Christiani
Feb 24, 2012·Metallomics : Integrated Biometal Science·Kanwal Rehman, Hua Naranmandura

❮ Previous
Next ❯

Citations

Jan 9, 2016·Critical Reviews in Food Science and Nutrition·Ilaria PaterniFilippo Minutolo
May 26, 2018·Annual Review of Nutrition·Anne K BozackMary V Gamble
Jul 3, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xiaofan XuMichelle A Mendez
Jun 8, 2018·International Journal of Environmental Research and Public Health·Poojitha BalakrishnanAna Navas-Acien
May 21, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Meytal ChernoffBrandon L Pierce
Feb 1, 2019·Environment International·Shangzhi GaoDavid C Christiani
Apr 8, 2021·Environmental Health Perspectives·Dayana A DelgadoBrandon L Pierce
Apr 28, 2021·Toxicology·Ahlam AbuawadMary V Gamble
Jul 13, 2021·Reviews on Environmental Health·Christiana KarachaliouIoannis Kalavrouziotis

❮ Previous
Next ❯

Methods Mentioned

BETA
chip
genotyping

Software Mentioned

Complex Trait Analysis ( GCTA )
EIGENSTRAT
wide
Genome
GCTA
PLINK
MaCH ( Markov Chain Haplotyping algorithm
Regional Genomic Relationship Mapping ( REACTA )
GREML
BEST

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.