TY - JOUR
T1 - Finding genomic function for genetic associations in nicotine addiction research
T2 - The ENCODE project's role in future pharmacogenomic analysis
AU - Vandenbergh, David J.
AU - Schlomer, Gabriel L.
N1 - Funding Information:
The authors would like to thank H. Harrington Cleveland, Kerry Hair, Will Horton, Helen Kamens, Marta Byrska-Bishop, and the members of the Vandenbergh lab for fruitful discussion and work that led to the ideas put forward in this work. This work was supported in part by a grant from the National Institute on Drug Abuse ( R01DA030389 ).
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.pbb.2014.01.009
DO - 10.1016/j.pbb.2014.01.009
M3 - Article
C2 - 24486638
AN - SCOPUS:84905283356
SN - 0091-3057
VL - 123
SP - 34
EP - 44
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
ER -