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Lipoprotein association studies: taking stock and moving forward

Talmud, PJ; Yiannakouris, N; Humphries, SE; (2011) Lipoprotein association studies: taking stock and moving forward. CURR OPIN LIPIDOL , 22 (2) 106 - 112. 10.1097/MOL.0b013e3283423f81.

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Purpose of reviewOver the last year, huge progress has been made using SNP arrays to identify genes associated with lipid traits.Recent findingsThe single genome-wide association studies (GWASs) may have reached a limit in identifying novel genes, but there has been tremendous progress from collaborative consortia examining pooled data from GWASs, often employing SNP imputation. For example, the Global Lipid Consortium reported that 56 of the 95 lipid-associated loci were novel to the pooled analysis from over 100 000 individuals. Complementary to this, a gene-centric approach, such as the 50K IBC HumanCVD chip, which provides deep coverage of approximately 2100 genes, has had success in ascertaining independently acting variants and helped us to move a step closer to identify functional variants. Yet irrespective of the platform used, for each trait, the percentage variance explained by these genes remains in the order of approximately 10-12% and it is still unclear to what extent rare mutations, identified by resequencing or exome sequencing approaches, or gene x gene and gene x environment studies, might boost this.SummaryGWAS-identified novel lipid-related loci highlight new pathways in lipid metabolism and may provide innovative drug targets. Furthermore, the use of lipid gene scores, over and above a single lipid measure, may have clinical utility.

Type: Article
Title: Lipoprotein association studies: taking stock and moving forward
DOI: 10.1097/MOL.0b013e3283423f81
Keywords: gene-centric chips, genome-wide association studies, HumanCVD chip, phenome scan, GENOME-WIDE ASSOCIATION, CORONARY-ARTERY-DISEASE, BLOOD-PRESSURE, RARE VARIANTS, WHOLE-GENOME, LIPID-LEVELS, RISK, LOCI
URI: http://discovery.ucl.ac.uk/id/eprint/763278
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