Review
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World J Cardiol. Jul 26, 2011; 3(7): 230-247
Published online Jul 26, 2011. doi: 10.4330/wjc.v3.i7.230
Implications of discoveries from genome-wide association studies in current cardiovascular practice
Panniyammakal Jeemon, Kerry Pettigrew, Christopher Sainsbury, Dorairaj Prabhakaran, Sandosh Padmanabhan
Panniyammakal Jeemon, Kerry Pettigrew, Christopher Sainsbury, Sandosh Padmanabhan, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, United Kingdom
Panniyammakal Jeemon, Dorairaj Prabhakaran, Centre for Chronic Disease Control, New Delhi, 110016, India
Panniyammakal Jeemon, Public Health Foundation of India, New Delhi, 110070, India
Dorairaj Prabhakaran, Centre for Cardiometabolic Risk Reduction Strategies, Centre of Excellence, Public Health Foundation of India, New Delhi, 110016, India
Author contributions: Jeemon P, Pettigrew K, Sainsbury C, Prabhakaran D and Padmanabhan S solely contributed to this paper; all authors reviewed and approved the final version.
Supported by A Wellcome Trust Capacity Strengthening Strategic Award to the Public Health Foundation of India and a consortium of UK universities (to Jeemon P); Research grants from National Heart Lung and Blood Institute, United States of America (HHSN286200900026C) and National Institute of Health, United States of America (1D43HD065249) (to Prabhakaran D)
Correspondence to: Sandosh Padmanabhan, PhD, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, United Kingdom. sandosh.padmanabhan@glasgow.ac.uk
Telephone: +44-141-3308428 Fax: +44-141-3306997
Received: April 29, 2011
Revised: July 2, 2011
Accepted: July 10, 2011
Published online: July 26, 2011
Abstract

Genome-wide association studies (GWAS) have identified several genetic variants associated with coronary heart disease (CHD), and variations in plasma lipoproteins and blood pressure (BP). Loci corresponding to CDKN2A/CDKN2B/ANRIL, MTHFD1L, CELSR2, PSRC1 and SORT1 genes have been associated with CHD, and TMEM57, DOCK7, CELSR2, APOB, ABCG5, HMGCR, TRIB1, FADS2/S3, LDLR, NCAN and TOMM40-APOE with total cholesterol. Similarly, CELSR2-PSRC1-SORT1, PCSK9, APOB, HMGCR, NCAN-CILP2-PBX4, LDLR, TOMM40-APOE, and APOC1-APOE are associated with variations in low-density lipoprotein cholesterol levels. Altogether, forty, forty three and twenty loci have been associated with high-density lipoprotein cholesterol, triglycerides and BP phenotypes, respectively. Some of these identified loci are common for all the traits, some do not map to functional genes, and some are located in genes that encode for proteins not previously known to be involved in the biological pathway of the trait. GWAS have been successful at identifying new and unexpected genetic loci common to diseases and traits, thus rapidly providing key novel insights into disease biology. Since genotype information is fixed, with minimum biological variability, it is useful in early life risk prediction. However, these variants explain only a small proportion of the observed variance of these traits. Therefore, the utility of genetic determinants in assessing risk at later stages of life has limited immediate clinical impact. The future application of genetic screening will be in identifying risk groups early in life to direct targeted preventive measures.

Keywords: Genome-wide association studies; Cardiovascular disease; Lipids; Blood pressure