Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank.

paper Cited Public

Authors: Wain, Louise V; Shrine, Nick; Miller, Suzanne; Jackson, Victoria E; Ntalla, Ioanna; Soler Artigas, María; Billington, Charlotte K; Kheirallah, Abdul Kader; Allen, Richard; Cook, James P; Probert, Kelly; Obeidat, Ma'en; Bossé, Yohan; Hao, Ke; Postma, Dirkje S; Paré, Peter D; Ramasamy, Adaikalavan; UK Brain Expression Consortium (UKBEC); Mägi, Reedik; Mihailov, Evelin; Reinmaa, Eva; Melén, Erik; O'Connell, Jared; Frangou, Eleni; Delaneau, Olivier; OxGSK Consortium; Freeman, Colin; Petkova, Desislava; McCarthy, Mark; Sayers, Ian; Deloukas, Panos; Hubbard, Richard; Pavord, Ian; Hansell, Anna L; Thomson, Neil C; Zeggini, Eleftheria; Morris, Andrew P; Marchini, Jonathan; Strachan, David P; Tobin, Martin D; Hall, Ian P
Year: 2015
Journal: The Lancet. Respiratory medicine
PMID: 26423011
DOI: 10.1016/S2213-2600(15)00283-0
PMCID: PMC4593935

BACKGROUND: Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of smoking behaviour and lung health. METHODS: We sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers. We developed a custom array for UK Biobank to provide optimum genome-wide coverage of common and low-frequency variants, dense coverage of genomic regions already implicated in lung health and disease, and to assay rare coding variants relevant to the UK population. We investigated whether there were shared genetic causes between different phenotypes defined by extremes of FEV1. We also looked for novel variants associated with extremes of FEV1 and smoking behaviour and assessed regions of the genome that had already shown evidence for a role in lung health and disease. We set genome-wide significance at p<5 × 10(-8). FINDINGS: UK Biobank participants were recruited from March 15, 2006, to July 7, 2010. Sample selection for the UK BiLEVE study started on Nov 22, 2012, and was completed on Dec 20, 2012. We selected 50,008 unique samples: 10,002 individuals with low FEV1, 10,000 with average FEV1, and 5002 with high FEV1 from each of the heavy smoker and never smoker groups. We noted a substantial sharing of genetic causes of low FEV1 between heavy smokers and never smokers (p=2.29 × 10(-16)) and between individuals with and without doctor-diagnosed asthma (p=6.06 × 10(-11)). We discovered six novel genome-wide significant signals of association with extremes of FEV1, including signals at four novel loci (KANSL1, TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported loci (NPNT and HLA-DQB1/HLA-DQA2). These variants also showed association with COPD, including in individuals with no history of smoking. The number of copies of a 150 kb region containing the 5' end of KANSL1, a gene that is important for epigenetic gene regulation, was associated with extremes of FEV1. We also discovered five new genome-wide significant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in brain tissue. INTERPRETATION: By sampling from the extremes of the lung function distribution in UK Biobank, we identified novel genetic causes of lung function and smoking behaviour. These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease. FUNDING: Medical Research Council.

#	Section	Preview
40	Discussion	The design of this genotyping array combined the best features of existing genome-wide platforms…
41	Discussion	is being used in the remaining roughly 450 000 UK Biobank participants. The UK Biobank array shares…
42	Discussion	Despite the strengths of using a large resource such as UK Biobank, this study has some limitations.…
43	Discussion	In summary, we show the usefulness in sampling from the extremes of UK Biobank data to identify…

Name	Type
1000 Genomes Project Phase 1 local	cohort
15q25 locus	variant
airflow obstruction	phenotype
airway disease local	phenotype
ANKK1	gene
asthma	phenotype
average FEV1 local	phenotype
Average percent predicted FEV1 local	phenotype
Bdnf	gene
brain	anatomy
brain tissue	anatomy
C20orf203 local	gene
C20orf203 SNP local	variant
case group	cohort
CCDC91 local	gene
chr12:114743533 local	variant
Chrna3	gene
Chrna4	gene
CHRNA5	gene
chronic obstructive pulmonary disease	phenotype
Common genetic variants (MAF>5%) local	variant
Complex structural variation region local	variant
control group	cohort
controls	cohort
COPD	phenotype
COPD cases local	cohort
CRHR1	gene
DBH	gene
discovery population local	cohort
DNA	drug
DNAH8 local	gene
Egfr	gene
Epigenetic mechanisms local	drug
European ancestry	cohort
European population	cohort
Extremes of FEV1 local	phenotype
fetal lung age local	phenotype
fetal lung development local	phenotype
FEV1 local	phenotype
FEV1 extremes local	phenotype
FEV1:FVC ratio local	phenotype
forced expiratory volume in 1 s (FEV1) local	phenotype
FVC local	phenotype
general population	cohort
General population cohorts local	cohort
genetic variants	cohort
genome-wide significant loci	cohort
Global Burden of Disease Study 2010 local	cohort
GOLD stage 2+ local	phenotype
GOLD Stage 2+ COPD local	phenotype
Grb2	gene
GSTCD local	gene
heavy drinking	phenotype
height	phenotype
high FEV1 local	phenotype
High FEV1 strata local	phenotype
high-income countries	cohort
High percent predicted FEV1 local	phenotype
HLA-DQA2	gene
HLA-DQB1 local	gene
HLA-DQB1/HLA-DQA2 common variant local	variant
independent discovery population local	cohort
independent target population local	cohort
Indoor air pollution local	drug
inhaled corticosteroid response local	phenotype
intergenic SNP near NCAM1 local	variant
INTS12 local	gene
inversion	variant
inversion 17q21.31 local	variant
KANSL1	gene
KIAA0195 local	gene
large biobank local	cohort
LLGL2 local	gene
low FEV1 local	phenotype
Low FEV1 local	phenotype
Low percent predicted FEV1 local	phenotype
LPPR5 local	gene
LRRC37A4P local	gene
lung function	phenotype
lung health and disease local	phenotype
Mapt	gene
medulla	anatomy
NCAM1	gene
never smokers	phenotype
Newly designed genotyping array local	drug
nicotine	drug
nicotine addiction	phenotype
nicotine dependence	phenotype
NOL4L local	gene
non-smoking individuals local	cohort
NPNT	gene
P3G Catalogue local	cohort
PABPC1P2 local	gene
participants without asthma local	cohort
percent predicted FEV1 local	phenotype
pulmonary fibrosis	phenotype
rare SNP on chromosome 12 local	variant
RBM19 local	gene
RBM19/TBX5 rare variant local	variant
reference panel	cohort
risk score local	drug
rs10193706 local	variant
rs10516526 local	variant
rs105165267 local	variant
rs12622738 local	variant
rs17843604 local	variant
rs2047409 local	variant
rs2532349 local	variant
rs34712979 local	variant
rs4466874 local	variant
rs6856422 local	variant
rs7218675 local	variant
rs7764819 local	variant
rs927334937 local	variant
rs9273359 local	variant
rs9274600 local	variant
rs953246 local	variant
RSRC1 local	gene
sentinel variant local	variant
SLMAP local	gene
smoking	phenotype
smoking behaviour	phenotype
smoking initiation	phenotype
smoking strata local	cohort
SNP_NCAM1_intron local	variant
SNP_trans_eQTL local	variant
Spirometry Data local	phenotype
substantia nigra	anatomy
target population	cohort
TBX5 local	gene
TET2	gene
TEX41 local	gene
tobacco use	phenotype
TSEN54 local	gene
TSEN54 common variant local	variant
TTC12	gene
UK10K	cohort
UK BiLEVE	cohort
UK BiLEVE array local	drug
UK Biobank	cohort
UK Biobank array local	drug
WDR61 local	gene
WHO Global Health Risks Report local	cohort
WNT3	gene

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TNS1 and NRXN1 Genes Interacting With Early-Life Smoking Exposure in Asthma-Plus-Eczema Susceptibility.	Margaritte-Jeannin P et al.	—	2023	→
Variation in <i>VEGFA</i> and risk of cardiovascular disease in the UK Biobank.	Chen H et al.	—	2023	→
A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome.	Skuladottir AT et al.	—	2022	→
Association of clonal hematopoiesis with chronic obstructive pulmonary disease.	Miller PG et al.	—	2022	→
Comprehensive identification of RNA transcripts and construction of RNA network in chronic obstructive pulmonary disease.	Liu P et al.	—	2022	→
Early-Life Exposure to Malnutrition From the Chinese Famine on Risk of Asthma and Chronic Obstructive Pulmonary Disease in Adulthood.	Jin C et al.	—	2022	→
Effect of Smoking on Lung Function Decline in a Retrospective Study of a Health Examination Population in Chinese Males.	Tian T et al.	—	2022	→
Evaluating the Effects of Diet-Gut Microbiota Interactions on Sleep Traits Using the UK Biobank Cohort.	Qi X et al.	—	2022	→
Genetic insights into smoking behaviours in 10,558 men of African ancestry from continental Africa and the UK.	Piga NN et al.	—	2022	→
Heritability Analyses Uncover Shared Genetic Effects of Lung Function and Change over Time.	Li D et al.	—	2022	→
Integration of questionnaire-based risk factors improves polygenic risk scores for human coronary heart disease and type 2 diabetes.	Tamlander M et al.	—	2022	→
Low depression frequency is associated with decreased risk of cardiometabolic disease.	Honigberg MC et al.	—	2022	→
Mechanisms of Lung Damage and Development of COPD Due to Household Biomass-Smoke Exposure: Inflammation, Oxidative Stress, MicroRNAs, and Gene Polymorphisms.	Ortiz-Quintero B et al.	—	2022	→
Metabolic Obesity Phenotypes and Risk of Lung Cancer: A Prospective Cohort Study of 450,482 UK Biobank Participants.	Shao F et al.	—	2022	→
miR-378 associated with proliferation, migration and apoptosis properties in A549 cells and targeted NPNT in COPD.	Qian G et al.	—	2022	→
Pathogenesis of chronic obstructive pulmonary disease: understanding the contributions of gene-environment interactions across the lifespan.	Agustí A et al.	—	2022	→
Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology.	Bjornsdottir G et al.	—	2022	→
Statin Use in Relation to Intraocular Pressure, Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank.	Kim J et al.	—	2022	→
The genetic architecture of language functional connectivity.	Mekki Y et al.	—	2022	→
The sequences of 150,119 genomes in the UK Biobank.	Halldorsson BV et al.	—	2022	→
White blood cells and chronic rhinosinusitis: a Mendelian randomization study.	Pongdee T et al.	—	2022	→
A combined genome-wide association and molecular study of age-related hearing loss in H. sapiens.	Liu W et al.	—	2021	→
A genome wide association study for lung function in the Korean population using an exome array.	Lee KS et al.	—	2021	→
A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo.	Skuladottir AT et al.	—	2021	→
A meta-analysis uncovers the first sequence variant conferring risk of Bell's palsy.	Skuladottir AT et al.	—	2021	→
An atlas of mitochondrial DNA genotype-phenotype associations in the UK Biobank.	Yonova-Doing E et al.	—	2021	→
A systematic analysis of protein-altering exonic variants in chronic obstructive pulmonary disease.	Moll M et al.	—	2021	→
Chronic lung diseases: prospects for regeneration and repair.	Barnes PJ et al.	—	2021	→
Elevated Blood Pressure Increases Pneumonia Risk: Epidemiological Association and Mendelian Randomization in the UK Biobank.	Zekavat SM et al.	—	2021	→
Genetic architecture of four smoking behaviors using partitioned SNP heritability.	Evans LM et al.	—	2021	→
Genetics of substance use disorders in the era of big data.	Gelernter J et al.	—	2021	→
Genetic variants associated with platelet count are predictive of human disease and physiological markers.	Mikaelsdottir E et al.	—	2021	→
Genome-wide association study of susceptibility to hospitalised respiratory infections.	Williams AT et al.	—	2021	→
Hedgehog interacting protein-expressing lung fibroblasts suppress lymphocytic inflammation in mice.	Yun JH et al.	—	2021	→
Integrating RNA-Seq With GWAS Reveals a Novel SNP in Immune-Related <i>HLA-DQB1</i> Gene Associated With Occupational Pulmonary Fibrosis Risk: A Multi-Stage Study.	Zhou Y et al.	—	2021	→
Interaction of Cigarette Smoking and Polygenic Risk Score on Reduced Lung Function.	Kim W et al.	—	2021	→
Intraocular Pressure, Glaucoma, and Dietary Caffeine Consumption: A Gene-Diet Interaction Study from the UK Biobank.	Kim J et al.	—	2021	→
Mapping pleiotropic loci using a fast-sequential testing algorithm.	Aguate FM et al.	—	2021	→
Mendelian randomization analysis of the association between human blood cell traits and uterine polyps.	Sun S et al.	—	2021	→
Pleiotropic associations of heterozygosity for the <i>SERPINA1</i> Z allele in the UK Biobank.	Fawcett KA et al.	—	2021	→
Predictors of lung function trajectories in population-based studies: A systematic review.	Okyere DO et al.	—	2021	→
Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function.	Yang T et al.	—	2021	→
Serum urate and lung cancer: a cohort study and Mendelian randomization using UK Biobank.	Horsfall LJ et al.	—	2021	→
Sex specific effect of gut microbiota on the risk of psychiatric disorders: A Mendelian randomisation study and PRS analysis using UK Biobank cohort.	Qi X et al.	—	2021	→
Sex-specific nicotine sensitization and imprinting of self-administration in rats inform GWAS findings on human addiction phenotypes.	Kozlova A et al.	—	2021	→
The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis.	Ivarsdottir EV et al.	—	2021	→
Tobacco Smoking and Risk for Pulmonary Fibrosis: A Prospective Cohort Study From the UK Biobank.	Bellou V et al.	—	2021	→
Variation in VKORC1 Is Associated with Vascular Dementia.	Mur J et al.	—	2021	→
White Matter Integrity and Nicotine Dependence: Evaluating Vertical and Horizontal Pleiotropy.	Ye Z et al.	—	2021	→
Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study.	AshaRani PV et al.	—	2021	→
A genome-wide multiphenotypic association analysis identified candidate genes and gene ontology shared by four common risky behaviors.	Ye J et al.	—	2020	→
Assessing thyroid cancer risk using polygenic risk scores.	Liyanarachchi S et al.	—	2020	→
Associations of Observational and Genetically Determined Caffeine Intake With Coronary Artery Disease and Diabetes Mellitus.	Said MA et al.	—	2020	→
Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts.	Moll M et al.	—	2020	→
Cognitive functioning and lifetime major depressive disorder in UK Biobank.	de Nooij L et al.	—	2020	→
DNA methylation-based measures of accelerated biological ageing and the risk of dementia in the oldest-old: a study of the Lothian Birth Cohort 1921.	Sibbett RA et al.	—	2020	→
Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis.	Olafsdottir TA et al.	—	2020	→
Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics.	Bovijn J et al.	—	2020	→
Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits.	Quach BC et al.	—	2020	→
Genetic regulation of gene expression of MIF family members in lung tissue.	Florez-Sampedro L et al.	—	2020	→
Genetics of COPD.	Silverman EK	—	2020	→
Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank.	Olafsdottir T et al.	—	2020	→
Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals.	Xu K et al.	—	2020	→
Genomic Regions 10q22.2, 17q21.31, and 2p23.1 Can Contribute to a Lower Lung Function in African Descent Populations.	Fonseca H et al.	—	2020	→
Identifying cross-disease components of genetic risk across hospital data in the UK Biobank.	Cortes A et al.	—	2020	→
Integrated genomics analysis highlights important SNPs and genes implicated in moderate-to-severe asthma based on GWAS and eQTL datasets.	Dong Z et al.	—	2020	→
Lung Development Genes and Adult Lung Function.	Portas L et al.	—	2020	→
Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.	Erzurumluoglu AM et al.	—	2020	→
Monogenic and polygenic inheritance become instruments for clonal selection.	Loh PR et al.	—	2020	→
On Genetics, Lung Developmental Biology, and Adult Lung Function.	Melén E et al.	—	2020	→
Pharmacogenetics of Pediatric Asthma: Current Perspectives.	Perez-Garcia J et al.	—	2020	→
Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis.	Oskarsson GR et al.	—	2020	→
Smoking, DNA Methylation, and Lung Function: a Mendelian Randomization Analysis to Investigate Causal Pathways.	Jamieson E et al.	—	2020	→
Stratifying major depressive disorder by polygenic risk for schizophrenia in relation to structural brain measures.	Harris MA et al.	—	2020	→
The dichotomous role of epiregulin in pain.	Verma V et al.	—	2020	→
The effects of age at menarche and first sexual intercourse on reproductive and behavioural outcomes: A Mendelian randomization study.	Lawn RB et al.	—	2020	→
Tobacco control policy and smoking among older Americans: An analysis of a nationally-representative longitudinal sample (1992-2014).	Kalousová L	—	2020	→
Translational Molecular Approaches in Substance Abuse Research.	Fulton SL et al.	—	2020	→
Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants.	Zhao X et al.	—	2020	→
A Genetic Risk Score Associated with Chronic Obstructive Pulmonary Disease Susceptibility and Lung Structure on Computed Tomography.	Oelsner EC et al.	—	2019	→
A loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis.	Kristjansson RP et al.	—	2019	→
Assessing potential shared genetic aetiology between body mass index and sleep duration in 142,209 individuals.	Garfield V et al.	—	2019	→
Association of alcohol consumption with allergic disease and asthma: a multi-centre Mendelian randomization analysis.	Skaaby T et al.	—	2019	→
Biological and clinical insights from genetics of insomnia symptoms.	Lane JM et al.	—	2019	→
Childhood and Parental Asthma, Future Risk of Bipolar Disorder and Schizophrenia Spectrum Disorders: A Population-Based Cohort Study.	Wu Q et al.	—	2019	→
Cohort Profile: Extended Cohort for E-health, Environment and DNA (EXCEED).	John C et al.	—	2019	→
Comment on the Relationship Between Common Variant Schizophrenia Liability and Number of Offspring in the UK Biobank.	Lawn RB et al.	—	2019	→
Common and Rare Variants Genetic Association Analysis of Cigarettes per Day Among Ever-Smokers in Chronic Obstructive Pulmonary Disease Cases and Controls.	Lutz SM et al.	—	2019	→
Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study.	Budu-Aggrey A et al.	—	2019	→
Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium.	Polimanti R et al.	—	2019	→
Genetic Advances in Chronic Obstructive Pulmonary Disease. Insights from COPDGene.	Ragland MF et al.	—	2019	→
Genetic architecture of human thinness compared to severe obesity.	Riveros-McKay F et al.	—	2019	→
Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.	Ferreira MAR et al.	—	2019	→
Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent.	Hübel C et al.	—	2019	→
Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.	Sakornsakolpat P et al.	—	2019	→
Genetic risk factors for the development of pulmonary disease identified by genome-wide association.	Hall R et al.	—	2019	→
Genetics and Gene-Environment Interactions in Childhood and Adult Onset Asthma.	Morales E et al.	—	2019	→
Genome analyses for the Tohoku Medical Megabank Project towards establishment of personalized healthcare.	Yasuda J et al.	—	2019	→
Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes.	Wang H et al.	—	2019	→
GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures.	Styrkarsdottir U et al.	—	2019	→
High-Throughput Sequencing in Respiratory, Critical Care, and Sleep Medicine Research. An Official American Thoracic Society Workshop Report.	Hersh CP et al.	—	2019	→
Identification of novel differentially methylated sites with potential as clinical predictors of impaired respiratory function and COPD.	Bermingham ML et al.	—	2019	→
Impact of Polygenic Risk for Schizophrenia on Cortical Structure in UK Biobank.	Neilson E et al.	—	2019	→
Inferring Multidimensional Rates of Aging from Cross-Sectional Data.	Pierson E et al.	—	2019	→
Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank.	Crawford K et al.	—	2019	→
Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study.	Shrine N et al.	—	2019	→
New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.	Shrine N et al.	—	2019	→
Power and Sample Size Calculations for Genetic Association Studies in the Presence of Genetic Model Misspecification.	Moore CM et al.	—	2019	→
Sequence variants associating with urinary biomarkers.	Benonisdottir S et al.	—	2019	→
Sequence variants with large effects on cardiac electrophysiology and disease.	Norland K et al.	—	2019	→
Sequence variation at ANAPC1 accounts for 24% of the variability in corneal endothelial cell density.	Ivarsdottir EV et al.	—	2019	→
Sex-specific moderation by lifestyle and psychosocial factors on the genetic contributions to adiposity in 112,151 individuals from UK Biobank.	Calvin CM et al.	—	2019	→
Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: genome-wide and transcriptome-wide studies.	Pividori M et al.	—	2019	→
The Korea Biobank Array: Design and Identification of Coding Variants Associated with Blood Biochemical Traits.	Moon S et al.	—	2019	→
Tobacco Genomics: Complexity and Translational Challenges.	Bergen AW et al.	—	2019	→
Adult height and risk of 50 diseases: a combined epidemiological and genetic analysis.	Lai FY et al.	—	2018	→
After asthma: redefining airways diseases.	Pavord ID et al.	—	2018	→
A Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos.	Burkart KM et al.	—	2018	→
An Exploratory Model of Psychosocial Factors and Healthy Habits in University Students of Physical Education Depending on Gender.	Chacón-Cuberos R et al.	—	2018	→
Are your covariates under control? How normalization can re-introduce covariate effects.	Pain O et al.	—	2018	→
Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study.	Trajanoska K et al.	—	2018	→
Associations of coffee genetic risk scores with consumption of coffee, tea and other beverages in the UK Biobank.	Taylor AE et al.	—	2018	→
Biomarkers: Delivering on the expectation of molecularly driven, quantitative health.	Wilson JL et al.	—	2018	→
Brugada Syndrome-Associated Genetic Loci Are Associated With J-Point Elevation and an Increased Risk of Cardiac Arrest.	Andreasen L et al.	—	2018	→
CHRNA5 and CHRNA3 polymorphism and lung cancer susceptibility in Palestinian population.	Ayesh BM et al.	—	2018	→
Coding variants in <i>RPL3L</i> and <i>MYZAP</i> increase risk of atrial fibrillation.	Thorolfsdottir RB et al.	—	2018	→
Collider scope: when selection bias can substantially influence observed associations.	Munafò MR et al.	—	2018	→
Dissecting respiratory disease heterogeneity through the genetics of diffusing capacity.	Hobbs BD et al.	—	2018	→
Ensemble genomic analysis in human lung tissue identifies novel genes for chronic obstructive pulmonary disease.	Morrow JD et al.	—	2018	→
Evaluation of the causal effects between subjective wellbeing and cardiometabolic health: mendelian randomisation study.	Wootton RE et al.	—	2018	→
Evolutionarily conserved <i>Tbx5</i>-<i>Wnt2/2b</i> pathway orchestrates cardiopulmonary development.	Steimle JD et al.	—	2018	→
Expanded genetic landscape of chronic obstructive pulmonary disease reveals heterogeneous cell type and phenotype associations	Sakornsakolpat P et al.	—	2018	—
Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.	Evangelou E et al.	—	2018	→
Genetic contributions to self-reported tiredness.	Deary V et al.	—	2018	→
Genetic contributions to Trail Making Test performance in UK Biobank.	Hagenaars SP et al.	—	2018	→
Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function.	Hagenaars SP et al.	—	2018	→
Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework.	Giuliani C et al.	—	2018	→
Genome-wide association meta-analysis yields 20 loci associated with gallstone disease.	Ferkingstad E et al.	—	2018	→
Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA.	Gudmundsson J et al.	—	2018	→
Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci.	Shah RL et al.	—	2018	→
Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence.	Hancock DB et al.	—	2018	→
Genome-wide association study for risk taking propensity indicates shared pathways with body mass index.	Clifton EAD et al.	—	2018	→
Genome-wide association study of lung function and clinical implication in heavy smokers.	Li X et al.	—	2018	→
GWAS on family history of Alzheimer's disease.	Marioni RE et al.	—	2018	→
Human Genetics of Addiction: New Insights and Future Directions.	Hancock DB et al.	—	2018	→
Human <i>CCL3L1</i> copy number variation, gene expression, and the role of the CCL3L1-CCR5 axis in lung function.	Adewoye AB et al.	—	2018	→
Influence of genetic variants on childhood lung function - The Generation R Study.	Shagiwal SS et al.	—	2018	→
Integrative genomics identifies new genes associated with severe COPD and emphysema.	Sakornsakolpat P et al.	—	2018	→
Meta-analysis of exome array data identifies six novel genetic loci for lung function.	Jackson VE et al.	—	2018	→
Meta-analysis of Icelandic and UK data sets identifies missense variants in SMO, IL11, COL11A1 and 13 more new loci associated with osteoarthritis.	Styrkarsdottir U et al.	—	2018	→
Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.	Wyss AB et al.	—	2018	→
Physical fitness and dementia risk in the very old: a study of the Lothian Birth Cohort 1921.	Sibbett RA et al.	—	2018	→
TET2: A Novel Epigenetic Regulator and Potential Intervention Target for Atherosclerosis.	Liu Y et al.	—	2018	→
The APOE ε4 allele is associated with a reduction in FEV1/FVC in women: A cross-sectional analysis of the Long Life Family Study.	Kulminski AM et al.	—	2018	→
The emerging role of NPNT in tissue injury repair and bone homeostasis.	Sun Y et al.	—	2018	→
The genetics of smoking in individuals with chronic obstructive pulmonary disease.	Obeidat M et al.	—	2018	→
The Overlap of Lung Tissue Transcriptome of Smoke Exposed Mice with Human Smoking and COPD.	Obeidat M et al.	—	2018	→
The UK Biobank resource with deep phenotyping and genomic data.	Bycroft C et al.	—	2018	→
The vitamin D binding protein axis modifies disease severity in lymphangioleiomyomatosis.	Miller S et al.	—	2018	→
Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits.	Rafnar T et al.	—	2018	→
Vascular inflammation and aortic stiffness: potential mechanisms of increased vascular risk in chronic obstructive pulmonary disease.	Fisk M et al.	—	2018	→
Age at menarche and lung function: a Mendelian randomization study.	Gill D et al.	—	2017	→
Bayesian analysis of genetic association across tree-structured routine healthcare data in the UK Biobank.	Cortes A et al.	—	2017	→
Can we predict the prognosis of COPD with a routine blood test?	Xiong W et al.	—	2017	→
Chronic obstructive pulmonary disease.	Rabe KF et al.	—	2017	→
Chronic Obstructive Pulmonary Disease Meta Genome-Wide Association Studies. New Insights into the Genetics of Chronic Obstructive Pulmonary Disease.	Rajput C	—	2017	→
Cognitive Performance Among Carriers of Pathogenic Copy Number Variants: Analysis of 152,000 UK Biobank Subjects.	Kendall KM et al.	—	2017	→
Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans.	Mitchell KA et al.	—	2017	→
Comparison of DNA quantification methodology used in the DNA extraction protocol for the UK Biobank cohort.	Welsh S et al.	—	2017	→
Does coffee consumption impact on heaviness of smoking?	Ware JJ et al.	—	2017	→
Do regional brain volumes and major depressive disorder share genetic architecture? A study of Generation Scotland (n=19 762), UK Biobank (n=24 048) and the English Longitudinal Study of Ageing (n=5766).	Wigmore EM et al.	—	2017	→
Early detection of COPD patients in GOLD 0 population: an observational non-interventional cohort study - MARKO study.	Vrbica Ž et al.	—	2017	→
Evidence for large-scale gene-by-smoking interaction effects on pulmonary function.	Aschard H et al.	—	2017	→
Female Smokers Are at Greater Risk of Airflow Obstruction Than Male Smokers. UK Biobank.	Amaral AFS et al.	—	2017	→
Genetic analysis in UK Biobank links insulin resistance and transendothelial migration pathways to coronary artery disease.	Klarin D et al.	—	2017	→
Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects.	Busch R et al.	—	2017	→
Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice.	Yadav P et al.	—	2017	→
Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.	Hobbs BD et al.	—	2017	→
Genetic Pleiotropy between Nicotine Dependence and Respiratory Outcomes.	Zhang J et al.	—	2017	→
Genetic polymorphism and chronic obstructive pulmonary disease.	Yuan C et al.	—	2017	→
Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study.	Allen RJ et al.	—	2017	→
Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.	Wain LV et al.	—	2017	→
Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.	Warren HR et al.	—	2017	→
Genome-wide association study on the FEV<sub>1</sub>/FVC ratio in never-smokers identifies HHIP and FAM13A.	van der Plaat DA et al.	—	2017	→
Heavier smoking increases coffee consumption: findings from a Mendelian randomization analysis.	Bjørngaard JH et al.	—	2017	→
Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium.	Skaaby T et al.	—	2017	→
Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness.	Willems SM et al.	—	2017	→
Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways.	Kheirallah AK et al.	—	2017	→
Microbial Diseases of Bivalve Mollusks: Infections, Immunology and Antimicrobial Defense.	Zannella C et al.	—	2017	→
Molecular genetic contributions to self-rated health.	Harris SE et al.	—	2017	→
Population-based imaging biobanks as source of big data.	Gatidis S et al.	—	2017	→
Progress in disease progression genetics: dissecting the genetic origins of lung function decline in COPD.	Busch R et al.	—	2017	→
Recent advances in understanding lung function development.	Melén E et al.	—	2017	→
Surfactant protein D is a causal risk factor for COPD: results of Mendelian randomisation.	Obeidat M et al.	—	2017	→
Targeted Sequencing of Lung Function Loci in Chronic Obstructive Pulmonary Disease Cases and Controls.	Artigas MS et al.	—	2017	→
Vagal innervation is required for pulmonary function phenotype in <i>Htr4<sup>-/-</sup></i> mice.	House JS et al.	—	2017	→
What do polymorphisms tell us about the mechanisms of COPD?	Li Y et al.	—	2017	→
ATS Core Curriculum 2016. Part IV. Adult Pulmonary Medicine Core Curriculum.	Michaud GC et al.	—	2016	→
Blurred lines. Eosinophilic COPD: ACOS or COPD phenotype?	Loureiro CC	—	2016	→
Development and the initial validation of a new self-administered questionnaire for an early detection of health status changes in smokers at risk for chronic obstructive pulmonary disease (MARKO questionnaire).	Vrbica Ž et al.	—	2016	→
Efficient Coalescent Simulation and Genealogical Analysis for Large Sample Sizes.	Kelleher J et al.	—	2016	→
Electronic Cigarettes for Curbing the Tobacco-Induced Burden of Noncommunicable Diseases: Evidence Revisited with Emphasis on Challenges in Sub-Saharan Africa.	Nansseu JR et al.	—	2016	→
Evaluation of Individuals at Risk for COPD: Beyond the Scope of the Global Initiative for Chronic Obstructive Lung Disease.	Antuni JD et al.	—	2016	→
Exome Sequencing Analysis in Severe, Early-Onset Chronic Obstructive Pulmonary Disease.	Qiao D et al.	—	2016	→
Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12.	Jackson VE et al.	—	2016	→
Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction.	Cadoni C	—	2016	→
Genetic determination of height-mediated mate choice.	Tenesa A et al.	—	2016	→
Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank.	Lane JM et al.	—	2016	→
Genome-wide association study of copy number variation with lung function identifies a novel signal of association near BANP for forced vital capacity.	Shrine N et al.	—	2016	→
Haplotype estimation for biobank-scale data sets.	O'Connell J et al.	—	2016	→
Lung Development and Aging.	Bush A	—	2016	→
Pleiotropy between neuroticism and physical and mental health: findings from 108 038 men and women in UK Biobank.	Gale CR et al.	—	2016	→
Rethinking the ethical approach to health information management through narration: pertinence of Ricœur's 'little ethics'.	Mouton Dorey C	—	2016	→
Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N=112 151) and 24 GWAS consortia.	Hagenaars SP et al.	—	2016	→
The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.	Astle WJ et al.	—	2016	→
The temporal relationship between poor lung function and the risk of diabetes.	Zaigham S et al.	—	2016	→
Translating Lung Function Genome-Wide Association Study (GWAS) Findings: New Insights for Lung Biology.	Kheirallah AK et al.	—	2016	→
Update in Chronic Obstructive Pulmonary Disease 2015.	Marchetti N et al.	—	2016	→
Variants near CHRNA3/5 and APOE have age- and sex-related effects on human lifespan.	Joshi PK et al.	—	2016	→
Elucidating COPD pathogenesis by large-scale genetic analyses.	Brusselle GG et al.	—	2015	→
Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation.	Soler Artigas M et al.	—	2015	→