Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2.

Scientific Reports
Jennifer J WareMarcus R Munafò

Abstract

Genome-wide association studies (GWAS) of complex behavioural phenotypes such as cigarette smoking typically employ self-report phenotypes. However, precise biomarker phenotypes may afford greater statistical power and identify novel variants. Here we report the results of a GWAS meta-analysis of levels of cotinine, the primary metabolite of nicotine, in 4,548 daily smokers of European ancestry. We identified a locus close to UGT2B10 at 4q13.2 (minimum p = 5.89 × 10(-10) for rs114612145), which was consequently replicated. This variant is in high linkage disequilibrium with a known functional variant in the UGT2B10 gene which is associated with reduced nicotine and cotinine glucuronidation activity, but intriguingly is not associated with nicotine intake. Additionally, we observed association between multiple variants within the 15q25.1 region and cotinine levels, all located within the CHRNA5-A3-B4 gene cluster or adjacent genes, consistent with previous much larger GWAS using self-report measures of smoking quantity. These results clearly illustrate the increase in power afforded by using precise biomarker measures in GWAS. Perhaps more importantly however, they also highlight that biomarkers do not always mark the phenotype ...Continue Reading

References

Mar 1, 1995·Preventive Medicine·E J Pérez-StableG Marín
Sep 1, 1993·American Journal of Public Health·M F VineR B Everson
Mar 1, 2005·Pharmacological Reviews·Janne HukkanenNeal L Benowitz
Aug 26, 2006·Drug and Alcohol Dependence·Andrew A StrasserEric A Feldman
Oct 13, 2006·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Viba MalaiyandiRachel F Tyndale
Apr 27, 2010·Nature Genetics·Thorgeir E ThorgeirssonKari Stefansson
Apr 27, 2010·Nature Genetics·Jason Z LiuJonathan Marchini
Apr 27, 2010·Nature Genetics·UNKNOWN Tobacco and Genetics Consortium
May 8, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Neal L BenowitzPeyton Jacob
May 27, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Jeannette Zinggeler BergSharon E Murphy
Jun 1, 2010·BMC Bioinformatics·Reedik Mägi, Andrew P Morris
Dec 21, 2010·American Journal of Human Genetics·Jian YangPeter M Visscher
Apr 27, 2012·Journal of the National Cancer Institute·Marcus R MunafòGeorge Davey Smith
Oct 5, 2012·Journal of Psychopharmacology·Ann McNeill, Marcus R Munafò
Feb 2, 2013·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Andy Z X ZhuRachel F Tyndale
Oct 9, 2014·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Yesha M PatelSharon E Murphy
May 28, 2015·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Julie-Anne TannerRachel F Tyndale

❮ Previous
Next ❯

Citations

Nov 1, 2016·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Leah S Richmond-RakerdIan R Gizer
May 5, 2017·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Nancy L SacconeUNKNOWN Genetics and Treatment Networks of the Society for Research on Nicotine and Tobacco (SRNT)
May 31, 2017·Addiction·Jennifer J WareMarcus R Munafò
Mar 6, 2018·Current Psychiatry Reports·Dana B HancockEric O Johnson
Apr 11, 2018·Respiratory Research·Ma'en ObeidatDon D Sin
Jul 3, 2018·International Journal of Epidemiology·Suzanne H GageMarcus R Munafò
Oct 31, 2018·Nature Genetics·Luke J O'Connor, Alkes L Price
Jan 9, 2019·Molecular Psychiatry·A Mesut ErzurumluogluJoanna M M Howson
May 11, 2016·Scientific Reports·Jingchun ChenUNKNOWN FTND meta-analysis group
Feb 14, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Adrien LabrietChantal Guillemette
Sep 9, 2019·European Journal of Epidemiology·Silvana C E MaasManfred Kayser
Aug 11, 2020·Schizophrenia Research and Treatment·Jingchun ChenXiangning Chen
Sep 28, 2018·CNS Drugs·Kevin P JensenMehmet Sofuoglu
Oct 3, 2018·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Jingchun ChenXiangning Chen
Dec 5, 2019·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Jaroslav A HubacekEva Kralikova
Oct 22, 2020·Nature Communications·Ke XuUNKNOWN VA Million Veteran Program
Jun 14, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Christopher J SipeSharon E Murphy
May 22, 2016·Neuroscience Letters·Li-Shiun ChenLaura Bierut
May 20, 2021·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Victoria A RisnerRohan H C Palmer

❮ Previous
Next ❯

Methods Mentioned

BETA
dissection
genotyping

Software Mentioned

GGZinGeest
GCTA
GWAMA
MACH
IMPUTE
IMPUTE2

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.