Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence.
- Authors
- Yoon, Dankyu; Kim, Young-Jin; Cui, Wen-Yan; Van der Vaart, Andrew; Cho, Yoon Shin; Lee, Jong-Young; Ma, Jennie Z; Payne, Thomas J; Li, Ming D; Park, Taesung
- Year
- 2012
- Journal
- Human genetics
- PMID
- 22006218
- DOI
- 10.1007/s00439-011-1102-x
- PMCID
- PMC4275569
Diseases related to smoking are the second leading cause of death in the world. Cigarette smoking is a risk factor for several diseases such as cancer and cardiovascular and respiratory disorders. Despite increasing evidence of genetic determination, the susceptibility genes and loci underlying various aspects of smoking behavior are largely unknown. Moreover, almost all reported genome-wide association studies (GWASs) have been performed on samples of European origin, limiting the applicability of the results to other ethnic populations. In this first GWAS on smoking behavior in an Asian population, after analyzing 8,842 DNA samples from the Korea Association Resource project with 352,228 single nucleotide polymorphisms (SNPs) genotyped for each sample, we identified 8 SNPs significantly associated with smoking initiation (SI) and 4 with nicotine dependence (ND). Because of the current unavailability of an independent Asian smoking sample, we replicated the discoveries in independent samples of European-American and African-American origin. Of the 12 SNPs examined in the replicated samples, we identified two SNPs, in the regulator of G-protein signaling 17 gene (rs7747583, p value(meta) = 6.40 × 10(-6); rs2349433, p value(meta) = 5.57 × 10(-6)), associated with SI. Also, we found two SNPs significantly associated with ND; one in the FERM domain containing 4A (rs4424567, p value(meta) = 2.30 × 10(-6)) and the other at 7q31.1 (rs848353, p value(meta) = 9.16 × 10(-8)). These SNPs represent novel targets for examination of smoking behavior and warrant further investigation using independent samples.
Chromosomal and QQ plots for smoking behaviors. Statistical significance of each SNP is scaled as −log10 (p value). Red dotted line indicates threshold in Discovery sample (p < 10—5), and blue dotted line indicates p value 10—4. We plotted the observed −log10-scaled association results versus −log10-scaled expected association results in QQ plots. Chromosomal and QQ plots for ND phenotype (a), SI-1 phenotype (b), and SI-2 phenotype (c)
Regional plots of significantly associated SNPs. We show the locus ±500 kb around the lead associated SNP. Statistical significance of each SNP is scaled as −log10 (p value) along the chromosomal position (NCBI build 36). The lead SNP at each locus is shown in a purple diamond. Direct genotyping in SNP genotyping chip is in a circle and imputed SNP in a square. Pairwise correlation between the lead and other SNPs at locus is shown on a scale from minimum (blue) to maximum (red). Estimated recombination rates from HapMap are plotted in aqua. The box below the association signals contains gene information within each locus. The direction of each gene is shown as a left or right arrow, and exon is shown as a filled square, whereas intron is indicated as a line. The LD pattern is at the bottom of each regional plot. A dotted line indicates the ±50-kb boundary from the lead SNP. The black circle stands for the position of the lead associated SNP. We show the LD pattern drawn from HapMap data for the European (CEU), African (YRI), and Asian (CHB/JPT) populations. R2 of SNPs is drawn on a scale from minimum (white) to maximum (red). Regional association plot for ND-associated SNPs, rs4424567 (a) and rs848353 (b) and SI-associated SNP, rs2349433 (c)
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| Comprehensive Analysis of the Gene Expression Profiles of Rat Brain Tissues under Environmental Exposure to Nicotine. | Liu W et al. | — | 2024 | → |
| Epigenetic and long-term effects of nicotine on biology, behavior, and health. | Gould TJ | — | 2023 | → |
| Identification of asthma-related genes using asthmatic blood eQTLs of Korean patients | Kim DJ et al. | — | 2023 | — |
| Associations between electronic devices use and common mental traits: A gene-environment interaction model using the UK Biobank data. | Ye J et al. | — | 2022 | → |
| Common and distinguishing genetic factors for substance use behavior and disorder: an integrated analysis of genomic and transcriptomic studies from both human and animal studies. | Chang XW et al. | — | 2022 | → |
| Novel risk factors for craniofacial microsomia and assessment of their utility in clinic diagnosis. | Xu X et al. | — | 2021 | → |
| Epigenetic Changes in Asthma: Role of DNA CpG Methylation. | Bae DJ et al. | — | 2020 | → |
| Identification of Functional Genetic Variants Associated With Alcohol Dependence and Related Phenotypes Using a High-Throughput Assay. | Thapa KS et al. | — | 2020 | → |
| Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose. | Wu P et al. | — | 2020 | → |
| Trend in the Prevalence of Non-Daily Smoking and Their Relationship with Mental Health Using the Korea Health and Nutrition Examination Survey. | Kwan Y et al. | — | 2020 | → |
| Adaptation to Extreme Environments in an Admixed Human Population from the Atacama Desert. | Vicuña L et al. | — | 2019 | → |
| An Exome-Wide Association Study Identifies New Susceptibility Loci for Age of Smoking Initiation in African- and European-American Populations. | Jiang K et al. | — | 2019 | → |
| Neurogenetic determinants and mechanisms of addiction to nicotine and smoked tobacco. | Sharp BM et al. | — | 2019 | → |
| Genetic Analysis of Rare Human Variants of Regulators of G Protein Signaling Proteins and Their Role in Human Physiology and Disease. | Squires KE et al. | — | 2018 | → |
| INAVA-ARNO complexes bridge mucosal barrier function with inflammatory signaling. | Luong P et al. | — | 2018 | → |
| A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents. | Maes HH et al. | — | 2017 | → |
| Aldehyde Dehydrogenase 2 Polymorphism Is a Predictor of Smoking Cessation. | Masaoka H et al. | — | 2017 | → |
| Combination of ALDH2 and ADH1B polymorphisms is associated with smoking initiation: A large-scale cross-sectional study in a Japanese population. | Masaoka H et al. | — | 2017 | → |
| Contrasting the effects of intra-uterine smoking and one-carbon micronutrient exposures on offspring DNA methylation. | Richmond RC et al. | — | 2017 | → |
| Pleiotropy of genetic variants on obesity and smoking phenotypes: Results from the Oncoarray Project of The International Lung Cancer Consortium. | Wang T et al. | — | 2017 | → |
| The genetic epidemiology of substance use disorder: A review. | Prom-Wormley EC et al. | — | 2017 | → |
| DNA methylation profiling in human lung tissue identifies genes associated with COPD. | Morrow JD et al. | — | 2016 | → |
| FRMD4A: A potential therapeutic target for the treatment of tongue squamous cell carcinoma. | Zheng X et al. | — | 2016 | → |
| Genetic Risk Scores Predict Recurrence of Acute Coronary Syndrome. | Vaara S et al. | — | 2016 | → |
| Hemizygous Deletion on Chromosome 3p26.1 Is Associated with Heavy Smoking among African American Subjects in the COPDGene Study. | Begum F et al. | — | 2016 | → |
| Increased expression of FERM domain-containing 4A protein is closely associated with the development of rectal cancer. | Fan Y et al. | — | 2016 | → |
| Maternal Smoking during Pregnancy and DNA-Methylation in Children at Age 5.5 Years: Epigenome-Wide-Analysis in the European Childhood Obesity Project (CHOP)-Study. | Rzehak P et al. | — | 2016 | → |
| Regulator of G Protein Signaling 17 as a Negative Modulator of GPCR Signaling in Multiple Human Cancers. | Hayes MP et al. | — | 2016 | → |
| A Genome-Wide Association Study Uncovers a Genetic Locus Associated with Thoracic-to-Hip Ratio in Koreans. | Cha S et al. | — | 2015 | → |
| Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies. | Nishizawa D et al. | — | 2015 | → |
| DNA methylation mediates the effect of maternal smoking during pregnancy on birthweight of the offspring. | Küpers LK et al. | — | 2015 | → |
| Genome-wide association studies in Africans and African Americans: expanding the framework of the genomics of human traits and disease. | Peprah E et al. | — | 2015 | → |
| Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence. | Hancock DB et al. | — | 2015 | → |
| Smoking-Associated Site-Specific Differential Methylation in Buccal Mucosa in the COPDGene Study. | Wan ES et al. | — | 2015 | → |
| Whole exome sequencing in females with autism implicates novel and candidate genes. | Butler MG et al. | — | 2015 | → |
| Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes. | Richardson TG et al. | — | 2014 | → |
| Genetics and smoking. | Loukola A et al. | — | 2014 | → |
| Genome-wide association study of smoking behaviours among Bangladeshi adults. | Argos M et al. | — | 2014 | → |
| Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample. | Loukola A et al. | — | 2014 | → |
| Identification of DNA methylation changes in newborns related to maternal smoking during pregnancy. | Markunas CA et al. | — | 2014 | → |
| Organic cation transporter variation and response to smoking cessation therapies. | Bergen AW et al. | — | 2014 | → |
| Prenatal tobacco smoke exposure is associated with childhood DNA CpG methylation. | Breton CV et al. | — | 2014 | → |
| Cigarette experimentation and the population attributable fraction for associated genetic and non-genetic risk factors. | Wilkinson AV et al. | — | 2013 | → |
| Comparison of the performance of two commercial genome-wide association study genotyping platforms in Han Chinese samples. | Jiang L et al. | — | 2013 | → |
| Gene × smoking interactions on human brain gene expression: finding common mechanisms in adolescents and adults. | Wolock SL et al. | — | 2013 | → |
| Significant association of CHRNB3 variants with nicotine dependence in multiple ethnic populations. | Cui WY et al. | — | 2013 | → |
| Phenotype prediction from genome-wide association studies: application to smoking behaviors. | Yoon D et al. | — | 2012 | → |
| The genetics of addiction. | Volkow ND et al. | — | 2012 | → |