Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes
Jingchun Chen1, Anu Loukola2,3, Nathan A Gillespie4
1Nevada Institute of Personalized Medicine, University of Nevada Las Vegas, Las Vegas, NV.
Summary
This study identified novel genetic candidates and biological pathways associated with nicotine dependence (ND) using genome-wide meta-analyses for the Fagerström test for nicotine dependence (FTND) and time to smoke first cigarette (TTFC). Further research into these findings can aid in developing effective smoking cessation treatments.
Area of Science:
- Genetics
- Pharmacology
- Neuroscience
Background:
- Nicotine dependence (ND) is a significant public health issue.
- The Fagerström test for nicotine dependence (FTND) and time to smoke first cigarette (TTFC) are key measures of ND.
- Genome-wide meta-analyses for these phenotypes have been limited.
Purpose of the Study:
- To conduct genome-wide meta-analyses for FTND and TTFC phenotypes.
- To identify novel genetic loci and biological pathways associated with ND.
- To provide a foundation for future research in smoking cessation.
Main Methods:
- Genome-wide meta-analyses were performed on adult smokers of European ancestry from 14 independent cohorts.
- Replication analyses were attempted for leading candidate loci.
- Gene-based and pathway analyses were conducted to explore biological mechanisms.
Main Results:
- Genome-wide significant associations were found for TTFC with loci on chromosomes 4q35, 11q22, and 14q21.
- Gene-based analyses identified associations for COPB2 with FTND, and TFCP2L1, RELN, and INO80C with TTFC.
- Pathway analyses implicated endocytosis, actin cytoskeleton regulation, axon guidance, MAPK, and chemokine signaling in ND.
Conclusions:
- Several promising genetic candidates and novel biological pathways involved in ND were identified.
- Some candidates (CHRNA4, THSD7B, RBFOX1, ZNF804A) showed links to other substance addictions and psychiatric disorders.
- Further verification of these candidates and pathways is necessary for developing effective prevention and treatment strategies.
Related Concept Videos
01:11Genome-wide Association Studies-GWAS
15.4K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
15.4K
02:02Genomics
39.8K
Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
39.8K
01:09Directing Effect of Substituents: meta-Directing Groups
5.8K
Substituents on the benzene ring that direct an incoming electrophile to undergo substitution at the meta position are called meta directors. All meta directors either have a positive charge on the atom directly bonded to the ring or a partial positive charge. These groups function by withdrawing electrons from the ring through inductive and resonance effects. Consider the carbocation intermediates formed upon the addition of an electrophile on nitrobenzene at the...
5.8K
02:30Genomic Imprinting and Inheritance
36.9K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
36.9K
03:21Genome Size and the Evolution of New Genes
9.0K
While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
9.0K
02:16Comparing Mitochondrial, Chloroplast, and Prokaryotic Genomes
15.3K
The present-day mitochondrial and chloroplast genomes have retained some of the characteristics of their ancestral prokaryotes and also have acquired new attributes during their evolution within eukaryotic cells. Like prokaryotic genomes, mitochondrial and chloroplast genomes neither bind with histone-like proteins nor show complex packaging into chromosome-like structures, as observed in eukaryotes. Unlike mitotic cell divisions observed in eukaryotic cells, mitochondria and chloroplasts...
15.3K