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Finding genomic function for genetic associations in nicotine addiction research: the ENCODE project's role in future pharmacogenomic analysis.

ABSTRACT: Tobacco-related behaviors and the underlying addiction to nicotine are complex tangles of genetic and environmental factors. Efforts to understand the genetic component of these traits have identified sites in the genome (single nucleotide polymorphisms, or SNPs) that might account for some part of the role of genetics in nicotine addiction. Encouragingly, some of these candidate SNPs remain significant in meta-analyses. However, genetic associations cannot be fully assessed, regardless of statistical significance, without an understanding of the functional consequences of the alleles present at these SNPs. The proper experimental test for allelic function can be very difficult to define, representing a roadblock in translating genetic results into treatment to prevent smoking and other nicotine-related behaviors. This roadblock can be navigated in part with a new web-based tool, the Encyclopedia of DNA Elements (ENCODE). ENCODE is a compilation of searchable data on several types of biochemical functions or "marks" across the genome. These data can be queried for the co-localization of a candidate SNP and a biochemical mark. The presence of a SNP within a marked region of DNA enables the generation of better-informed hypotheses to test possible functional roles of alleles at a candidate SNP. Two examples of such co-localizations are presented. One example reveals ENCODE's ability to relate a candidate SNP's function with a gene very far from the physical location of the SNP. The second example reveals a new potential function of the SNP, rs4105144, that has been genetically associated with the number of cigarettes smoked per day. Details for accessing the ENCODE data for this SNP are provided to serve as a tutorial. By serving as a bridge between genetic associations and biochemical function, ENCODE has the power to propel progress in untangling the genetic aspects of nicotine addiction - a major public health concern.

SUBMITTER: Vandenbergh DJ

PROVIDER: S-EPMC4117825 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Finding genomic function for genetic associations in nicotine addiction research: the ENCODE project's role in future pharmacogenomic analysis.

Vandenbergh David J DJ Schlomer Gabriel L GL

Pharmacology, biochemistry, and behavior 20140131

Tobacco-related behaviors and the underlying addiction to nicotine are complex tangles of genetic and environmental factors. Efforts to understand the genetic component of these traits have identified sites in the genome (single nucleotide polymorphisms, or SNPs) that might account for some part of the role of genetics in nicotine addiction. Encouragingly, some of these candidate SNPs remain significant in meta-analyses. However, genetic associations cannot be fully assessed, regardless of stati ...[more]

PMID: 24486638

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Project description:South Africa, like many other developing countries, stands to benefit from novel diagnostics and drugs developed by pharmacogenomics guidance due to high prevalence of disease burden in the region. This includes both communicable (e.g., HIV/AIDS and tuberculosis) and non-communicable (e.g., diabetes and cardiovascular) diseases. For example, although only 0.7% of the world's population lives in South Africa, the country carries 17% of the global HIV/AIDS burden and 5% of the global tuberculosis burden. Nobel Peace Prize Laureate Archbishop Emeritus Desmond Tutu has coined the term Rainbow Nation, referring to a land of wealth in its many diverse peoples and cultures. It is now timely and necessary to reflect on how best to approach new genomics biotechnologies in a manner that carefully considers the public health needs and extant disease burden in the region. The aim of this paper is to document and review the advances in pharmacogenomics in South Africa and importantly, to evaluate the direction that future research should take. Previous research has shown that the populations in South Africa exhibit unique allele frequencies and novel genetic variation in pharmacogenetically relevant genes, often differing from other African and global populations. The high level of genetic diversity, low linkage disequilibrium and the presence of rare variants in these populations question the feasibility of the use of current commercially available genotyping platforms, and may partially account for genotype-phenotype discordance observed in past studies. However, the employment of high throughput technologies for genomic research, within the context of large clinical trials, combined with interdisciplinary studies and appropriate regulatory guidelines, should aid in acceleration of pharmacogenomic discoveries in high priority therapeutic areas in South Africa. Finally, we suggest that projects such as the H3Africa Initiative, the SAHGP and PGENI should play an integral role in the coordination of genomic research in South Africa, but also other African countries, by providing infrastructure and capital to local researchers, as well as providing aid in addressing the computational and statistical bottlenecks encountered at present.

Dataset Information

Finding genomic function for genetic associations in nicotine addiction research: the ENCODE project's role in future pharmacogenomic analysis.

Publications

Finding genomic function for genetic associations in nicotine addiction research: the ENCODE project's role in future pharmacogenomic analysis.

Similar Datasets

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