The shared genetic architectures between lung cancer and multiple polygenic phenotypes in genome-wide association studies

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

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Shared genetic etiology of hypertension and stroke: evidence from bioinformatics analysis of genome-wide association studies

Journal of Human Hypertension ◽

10.1038/s41371-017-0012-3 ◽

2017 ◽

Vol 32 (1) ◽

pp. 34-39 ◽

Cited By ~ 1

Author(s):

LD Ji ◽

SP Hu ◽

JY Li ◽

BB Yao ◽

QJ Shen ◽

...

Keyword(s):

Bioinformatics Analysis ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genetic Etiology ◽

Genome Wide ◽

Shared Genetic

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Abstract 2568: Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women

10.1158/1538-7445.am2016-2568 ◽

2016 ◽

Author(s):

Qing Lan ◽

Zhaoming Wang ◽

Wei Jie Seow ◽

Kouya Shiraishi ◽

Hongbing Shen ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Susceptibility ◽

Association Studies ◽

Meta Analysis ◽

Genome Wide Association ◽

Asian Women ◽

Genome Wide Association Studies ◽

Susceptibility Loci ◽

Genome Wide ◽

Lung Cancer Susceptibility

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Genetic polymorphisms and lung cancer risk: Evidence from meta-analyses and genome-wide association studies

Lung Cancer ◽

10.1016/j.lungcan.2017.08.026 ◽

2017 ◽

Vol 113 ◽

pp. 18-29 ◽

Cited By ~ 13

Author(s):

Caiyang Liu ◽

Huijie Cui ◽

Dongqing Gu ◽

Min Zhang ◽

Yanfei Fang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Genetic Polymorphisms ◽

Lung Cancer Risk ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Meta Analyses

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Empirical Hierarchical Bayes Approach to Gene-Environment Interactions: Development and Application to Genome-Wide Association Studies of Lung Cancer in TRICL

Genetic Epidemiology ◽

10.1002/gepi.21741 ◽

2013 ◽

Vol 37 (6) ◽

pp. 551-559 ◽

Cited By ~ 5

Author(s):

Melanie Sohns ◽

Elena Viktorova ◽

Christopher I. Amos ◽

Paul Brennan ◽

Gord Fehringer ◽

...

Keyword(s):

Lung Cancer ◽

Association Studies ◽

Hierarchical Bayes ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Gene Environment ◽

Genome Wide ◽

Bayes Approach

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A large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic etiology with obesity

European Respiratory Journal ◽

10.1183/13993003.00199-2021 ◽

2021 ◽

pp. 2100199

Author(s):

Zhaozhong Zhu ◽

Jiachen Li ◽

Jiahui Si ◽

Baoshan Ma ◽

Huwenbo Shi ◽

...

Keyword(s):

Lung Function ◽

Large Scale ◽

Causal Effect ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genetic Etiology ◽

Trait Analysis ◽

Genome Wide ◽

Shared Genetic

Lung function is a heritable complex phenotype with obesity being one of its important risk factors. However, the knowledge of their shared genetic basis is limited. Most genome-wide association studies (GWASs) for lung function have been based on European populations, limiting the generalisability across populations. Large-scale lung function GWAS in other populations are lacking.We included 100 285 subjects from China Kadoorie Biobank (CKB). To identify novel loci for lung function, single-trait GWAS were performed on FEV1, FVC, FEV1/FVC in CKB. We then performed genome-wide cross-trait analysis between the lung function and obesity traits (body mass index [BMI], BMI-adjusted waist-to-hip ratio, and BMI-adjusted waist circumference) to investigate the shared genetic effects in CKB. Finally, polygenic risk scores (PRSs) of lung function were developed in CKB and its interaction with BMI's association on lung function were examined. We also conducted cross-trait analysis in parallel with CKB using 457 756 subjects from UK Biobank (UKB) for replication and investigation of ancestry specific effect.We identified 9 genome-wide significant novel loci for FEV1, 6 for FVC and 3 for FEV1/FVC in CKB. FEV1 and FVC showed significant negative genetic correlation with obesity traits in both CKB and UKB. Genetic loci shared between lung function and obesity traits highlighted important pathways, including cell proliferation, embryo and tissue development. Mendelian randomisation analysis suggested significant negative causal effect of BMI on FEV1 and on FVC in both CKB and UKB. Lung function PRSs significantly modified the effect of change-in-BMI on change-in-lung function during an average follow-up of 8 years.This large-scale GWAS of lung function identified novel loci and shared genetic etiology between lung function and obesity. Change-in-BMI might affect change-in-lung function differently according to a subject's polygenic background. These findings may open new avenue for the development of molecular-targeted therapies for obesity and lung function improvement.

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