Volume 381, Issue 9874, Pages (April 2013)

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Volume 381, Issue 9874, Pages 1293-1301 (April 2013) Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study Prof Philippa J Talmud, DSc, Sonia Shah, MSc, Ros Whittall, MSc, Marta Futema, BSc, Philip Howard, BSc, Jackie A Cooper, MSc, Seamus C Harrison, MRCS, KaWah Li, MSc, Fotios Drenos, PhD, Frederik Karpe, PhD, Prof H Andrew W Neil, DSc, Olivier S Descamps, PhD, Claudia Langenberg, PhD, Nicholas Lench, PhD, Prof Mika Kivimaki, PhD, Prof John Whittaker, PhD, Prof Aroon D Hingorani, PhD, Meena Kumari, PhD, Prof Steve E Humphries, PhD The Lancet Volume 381, Issue 9874, Pages 1293-1301 (April 2013) DOI: 10.1016/S0140-6736(12)62127-8 Copyright © 2013 Elsevier Ltd Terms and Conditions

Figure 1 Risk ratio of participants in the WHII population having LDL-C >4·9 mmol/L according to gene score decile LDL-C=low-density lipoprotein cholesterol. WHII=Whitehall II. *Decile 1 used as reference. The Lancet 2013 381, 1293-1301DOI: (10.1016/S0140-6736(12)62127-8) Copyright © 2013 Elsevier Ltd Terms and Conditions

Figure 2 Distribution of weighted LDL-C gene scores (A) Whitehall II controls (WHII) versus patients with familial hypercholesterolaemia without a known mutation (FH/M–). (B) WHII controls versus patients with familial hypercholesterolaemia with a known mutation (FH/M+). (C) FH/M– versus FH/M+. In both patients with definite familial hypercholesterolaemia (DFH) and those with possible familial hypercholesterolaemia (PFH), patients without a detected mutation had a significantly higher mean weighted LDL-C gene score than did those with a detected mutation (DFH/M+ 0·95 [SD 0·012] vs DFH/M– 1·03 [0·018], p=0·001; PFH/M+ 0·91 [0·043] vs PFH/M– 1·00 [0·015], p=0·03; appendix). LDL-C=low-density lipoprotein cholesterol. The Lancet 2013 381, 1293-1301DOI: (10.1016/S0140-6736(12)62127-8) Copyright © 2013 Elsevier Ltd Terms and Conditions

Figure 3 Diagnostic workflow for cascade testing in patients with familial hypercholesterolaemia FH=familial hypercholesterolaemia. SNP=single nucleotide polymorphism. LDL-C=low-density lipoprotein cholesterol. *As recommended by NICE.27 The Lancet 2013 381, 1293-1301DOI: (10.1016/S0140-6736(12)62127-8) Copyright © 2013 Elsevier Ltd Terms and Conditions