LDL-cholesterol concentrations: a genome-wide association study

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LDL-cholesterol concentrations: a genome-wide association study Dr Manjinder S Sandhu, PhD, Dawn M Waterworth, PhD, Sally L Debenham, PhD, Eleanor Wheeler, PhD, Konstantinos Papadakis, MSc, Jing Hua Zhao, PhD, Kijoung Song, PhD, Xin Yuan, PhD, Toby Johnson, PhD, Sofie Ashford, BSc, Michael Inouye, MSc, Robert Luben, BSc, Matthew Sims, BSc, David Hadley, MSc, Wendy McArdle, PhD, Prof Philip Barter, PhD, Prof Y Antero Kesäniemi, PhD, Prof Robert W Mahley, PhD, Prof Ruth McPherson, FRCP, Prof Scott M Grundy, PhD, Prof Sheila A Bingham, PhD, Prof Kay-Tee Khaw, FRCP, Ruth JF Loos, PhD, Prof Gérard Waeber, MD, Inês Barroso, PhD, Prof David P Strachan, MD, Panagiotis Deloukas, PhD, Peter Vollenweider, MD, Prof Nicholas J Wareham, FRCP, Vincent Mooser, MD The Lancet Volume 371, Issue 9611, Pages 483-491 (February 2008) DOI: 10.1016/S0140-6736(08)60208-1 Copyright © 2008 Elsevier Ltd Terms and Conditions

Figure 1 Linkage disequilibrium plot (A) Plot of 98 kb genomic region aligned with association signals for imputed SNPs. Positions of genes, SNPs genotyped in HapMap, and linkage disequilibrium among SNPs (r2 is shown). r2 values of 1·0 are depicted by red diamonds, intermediate r2 values are represented in pink, and r2 values of 0 as white. Aligned underneath the linkage disequilibrium plot is a graph showing the association signal for each of the 71 SNPs which could be imputed from our data. The plot was generated with HapMap (release 22/phase II Apr 07, NCBI B36 assembly, dbSNP build 126, [CEPH Utah trios], chr1 co-ordinates 109541887-109640441). This plot illustrates that the strongest association signals are localised to a 14 kb region shown in detail in (B). Imputed SNPs that were statistically associated with circulating concentrations of LDL cholesterol at the genome-wide level (p<1·0×10−7) are boxed. The Lancet 2008 371, 483-491DOI: (10.1016/S0140-6736(08)60208-1) Copyright © 2008 Elsevier Ltd Terms and Conditions

Figure 2 Association between SNPs at the 1p13.3 locus and circulating concentrations of LDL cholesterol For individual studies β coefficients are depicted by black boxes and spanned by 95% CI. Diamonds represent overall β coefficients for each SNP and the width of the diamonds delineate their 95% CI. Corresponding values for each independent study and for the overall estimate are given to the right of the plot. The Lancet 2008 371, 483-491DOI: (10.1016/S0140-6736(08)60208-1) Copyright © 2008 Elsevier Ltd Terms and Conditions