1. Update on Genetics in Hypertension Christian Delles BHF Glasgow Cardiovascular Research Centre Institute of Cardiovascular and Medical Sciences University of Glasgow

2. Cardiovascular Continuum Twin studies, pedigree studies BP variability attributable to all genetic factors: 25% to 65% Heritability ( h 2 ) Fraction of variation in disease susceptibility due to genetic factors: Systolic BP 15-40%, diastolic BP 15-30% Sibling recurrent risk ( s) Degree of elevated risk of disease for a sibling of an affected individual compared with a member of the general population: Hypertension around 1.2–1.5 Heritability Padmanabhan S et al. J Hypertens 2008

3. Cardiovascular Continuum Distribution of Blood Pressure in the Population Analysis of the Third National Health and Nutrition Examination Survey, 1988-1994

4. Cardiovascular Continuum The Platt vs Pickering Debate George PickeringRobert Platt National Portrait Gallery, London

5. Cardiovascular Continuum The Platt vs Pickering Debate Delles C. Genetics of Hypertension. Future Medicine 2013 PickeringPlatt

6. Monogenic Traits Deutsche Bundespost

7. Thomas SR 2009 Monogenic Forms of Hypertension

8. Padmanabhan S et al. Trends Genet 2012 … cont.

9. Monogenic Forms of Hypertension Padmanabhan S et al. Trends Genet 2012 … cont.

10. Padmanabhan S et al. J Hypertens 2008 The Platt vs Pickering Debate

11. Monogenic Traits Definition of the phenotype

12. Cardiovascular Continuum Distribution of Blood Pressure in the Population Analysis of the Third National Health and Nutrition Examination Survey, 1988-1994

13. Cardiovascular Continuum Definition of Hypertension ESH/ESC Guidelines. J Hypertens 2013

14. Cardiovascular Continuum Qualitative vs Quantitative Trait 139/80 mmHg 141/80 mmHg 100/60 mmHg 200/120 mmHg Quantitative trait 139/80 mmHg 141/80 mmHg 140/90 mmHg Qualitative trait NormotensiveHypertensive

15. Study Designs Delles C. Genetics of Hypertension. Future Medicine 2013

16. Cardiovascular Continuum Blood Pressure The measurement [of blood pressure] is likely the clinical procedure of greatest importance that is performed in the sloppiest manner. Norman Kaplan. Am J Hypertens 1998

17. Cardiovascular Continuum Ambulatory Blood Pressure Monitoring Precise assessment of blood pressure Better determinant of hypertension-related organ damage Detection of white coat hypertension Detection of masked hypertension

18. Cardiovascular Continuum PAMELA Study Padmanabhan S et al. J Hypertens 2010

19. Monogenic Traits Candidate gene studies

20. Cardiovascular Continuum Renin-Angiotensin-Aldosterone System Rad A 2006

22. Cardiovascular Continuum CYP11B2 and Hypertension Sookoian S et al. J Hypertens 2007

23. Monogenic Traits Genome wide association studies

24. Genomics Genomics is the study of an organism's entire genome. "Unbiased" (hypothesis-free) approach

25. Genome-wide Arrays IlluminaAffymetrix

26. Wellcome Trust Case-Control Consortium WTCCC. Nature 2007

27. Cases and Controls in WTCCC

28. WTCCC. Nature 2007 Crohn’s Disease -log P -value

29. WTCCC. Nature 2007

30. Global BPGen Newton-Cheh C et al. Nat Genet 2009

31. Global BPgen Study: 34,433 Subjects Newton-Cheh C et al. Nat Genet 2009

32. Global BPgen Study: 34,433 Subjects Newton-Cheh C et al. Nat Genet 2009

33. Relationship of SNPs to Blood Pressure Traits Newton-Cheh C et al. Nat Genet 2009

34. International Consortium for BP GWAS International Consortium for Blood Pressure Genome-Wide Association Studies. Nature 2011

35. 200,000 Individuals: 16 Novel Loci International Consortium for Blood Pressure Genome-Wide Association Studies. Nature 2011

36. Monogenic Traits GWAS into the extremes of blood pressure