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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ESingle nucleotide polymorphisms (SNP) are useful for comparing regions of the genome between cohorts with and without a particular disease. There are six diseases that have an extensive genomic definition: type 2 diabetes, Crohn\u0027s disease, breast cancer, age-related macular degeneration, prostate cancer, and systemic lupus erythematosus. Of particular interest to cardiologists, SNPs have been defined for myocardial infarction, coronary artery disease, atrial fibrillation, lipoprotein disorders, and hypercholesterolemia.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiology genomics\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/2\/4\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2020567950\u0022 data-figure-caption=\u0022\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure1\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/2\/4\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/2\/4\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure1\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/2\/4\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11112\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-2\u0022\u003EAlthough the June 2000 New York Times headline, \u201cGenetic Code of Human Life is Cracked by Scientists,\u201d appeared to herald the arrival of the \u2018genetic age,\u2019 according to Eric J. Topol, MD, Scripps Translational Science Institute, La Jolla, CA, it has been the numerous and stunning breakthroughs in single nucleotide polymorphisms (SNP) in the last year that has ushered in the \u201cage of the genome.\u201d A SNP is a DNA sequence variation that occurs when a single nucleotide differs between members of a species in at least 1% of the population. SNPs are useful for comparing regions of the genome between cohorts with and without a particular disease.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EThe identification of SNPs has created a \u2018genomic gold rush\u2019 to discover associations between a disease process and SNP variants. Over 40 diseases have undergone genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease. In a GWAS that was undertaken in the British population that examined approximately 2000 individuals for each of seven major diseases and a shared set of approximately 3000 controls, 24 independent association signals at P \u0026lt; 5 \u00d7 10\u003Csup\u003E-7\u003C\/sup\u003E were identified, including one in bipolar disorder, one in coronary artery disease, nine in Crohn\u0027s disease, three in rheumatoid arthritis, seven in type 1 diabetes, and three in type 2 diabetes [Wellcome Trust Case Control Consortium. \u003Cem\u003ENature\u003C\/em\u003E 2007].\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EWhole genome information, when combined with clinical and other phenotype data, offers the potential for increased understanding of basic biological processes that affect human health, improve risk prediction, disease prevention, and patient care. Ultimately, the realization of the promise of personalized medicine, which Dr. Topol believes will be readily available by the year 2015, would permit clinicians to deliver optimal therapies to their patients.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThere are six diseases that have an extensive genomic definition: type 2 diabetes, Crohn\u0027s disease, breast cancer, age-related macular degeneration, prostate cancer, and systemic lupus erythematosus. Of particular interest to cardiologists, SNPs have been defined for myocardial infarction (MI), coronary artery disease (CAD), atrial fibrillation (AF), lipoprotein disorders, and hypercholesterolemia.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003ETwo common sequence variants on chromosome 9p21, tagged by rs10757278-G and rs10811661-T, affect the risk of MI [Helgadottir A et al. \u003Cem\u003EScience\u003C\/em\u003E 2007]. Approximately 21% of individuals in the population are homozygous for these variants, and their estimated risk of suffering an MI is 1.64 times as great as that of non-carriers. The same sequence variant on 9p21 that is associated with MI is also associated with abdominal aortic aneurysms and intracranial aneurysms [Helgadottir A et al. \u003Cem\u003ENat Genet\u003C\/em\u003E 2008]. However, to date there are no studies that show how these markers develop into the disease state.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EAnother recent GWAS has identified variants on chromosome 9p21.3 that affect the risk of CAD. The risk allele (C) of the lead SNP, rs1333049, was significantly associated with CAD (p\u0026lt;0.05). In a pooled analysis, the odds ratio per copy of the risk allele was 1.29 (95% CI, 1.22 to 1.37; p=0.0001). An autosomal-additive mode of inheritance best explained the underlying association [Schunkert H et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2008].\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003ETwo sequence variants on chromosome 4q25 that are adjacent to PITX2 (which has a critical function in left-right asymmetry of the heart) confer risk of A F. The association is inversely related to age. About 35% of individuals of European descent have at least one of the variants, and the risk of AF increases by 1.72 and 1.39 per copy [Gudbjartsson DF et al. \u003Cem\u003ENature\u003C\/em\u003E 2007]. Nine validated SNP variants on chromosome 1p13.3 have been associated with modulation in levels of LDL or HDL cholesterol, and the incorporation of them into a genotype score improved clinical risk reclassification in a cardiovascular cohort when added to standard clinical factors [Kathiresan S et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008; Sandhu MS et al. \u003Cem\u003ELancet\u003C\/em\u003E 2008].\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EDr. Topol believes that this \u2018treasure trove\u2019 of genetically linked lipoprotein biology may lead to novel therapeutic interventions if a few caveats can be overcome. He cautioned that we are still working with incomplete coverage of the genome and that structural variants are complex and much larger than initially hypothesized [Korbel JO et al. \u003Cem\u003EScience\u003C\/em\u003E 2007]. Structural variation of the genome involves kilobase- to megabase-sized deletions, duplications, insertions, inversions, and complex combinations of rearrangements. Epigenomics (processes that regulate how and when genes change) and epistasis (when the action of one gene is modified by one or more genes) are not completely understood and may impact the disease process in unpredictable ways. In many cases, the observed effects actually result from multiple SNPs that act in concert within a gene, and thus analysis of a few variants per gene is not likely to be sufficient to identify potential functional effects.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003ENonetheless, the \u2018age of the genome\u2019 is truly upon us, with private companies beginning to offer genome \u201cscans\u201d that claim to have the ability to predict the risk of many types of diseases. Next to come will be a consumer genome movement and genetic home testing kits. The physician needs to be prepared for the day when patients begin showing up in their offices with individual SNP profiles asking for interpretation of their health risk factors. Dr. Topol\u0027s final comment was presented in a slide titled \u201cThe Resequencing Imperative\u201d\u2014\u201c..when genome-wide resequencing is practical and affordable, it will be increasingly difficult for the genomic basis of health and disease to be left undetected.\u201d\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2008 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/8\/2\/4.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzmfsd\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmfsd\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}