update on genetics in hypertension christian delles bhf glasgow cardiovascular research centre...
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Update on Genetics in Hypertension
Christian Delles
BHF Glasgow Cardiovascular Research CentreInstitute of Cardiovascular and Medical SciencesUniversity of Glasgow
Cardiovascular Continuum
Twin studies, pedigree studiesBP variability attributable to all genetic factors: 25% to 65%
Heritability (h2)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
Cardiovascular ContinuumDistribution of Blood Pressure in the Population
Analysis of the Third National Health and Nutrition Examination Survey, 1988-1994
Cardiovascular ContinuumThe Platt vs Pickering Debate
George Pickering Robert Platt
National Portrait Gallery, London
Cardiovascular ContinuumThe Platt vs Pickering Debate
Delles C. Genetics of Hypertension. Future Medicine 2013
Pickering Platt
Cardiovascular ContinuumDistribution of Blood Pressure in the Population
Analysis of the Third National Health and Nutrition Examination Survey, 1988-1994
Cardiovascular ContinuumQualitative vs Quantitative Trait
139/80mmHg
141/80mmHg
100/60mmHg
200/120mmHg
Quantitative trait
139/80mmHg
141/80mmHg
140/90 mmHg
Qualitative trait
Normotensive Hypertensive
Cardiovascular ContinuumBlood 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
Cardiovascular ContinuumAmbulatory Blood Pressure Monitoring
• Precise assessment of blood pressure• Better determinant of hypertension-related organ damage• Detection of white coat hypertension• Detection of masked hypertension
Genomics
Genomics is the study of an organism's entire
genome.
"Unbiased" (hypothesis-free) approach
WTCCC. Nature 2007
Cases and Controls in WTCCC
Collection 58C UKBS BD CAD CD HT RA T1D T2D No Samples 1480 1458 1868 1926 1748 1952 1860 1963 1924 % Male / %Female
50/50 48/52 37/63 79/21 39/61 40/60 25/75 51/49 58/42
Eastern 11 12 3 10 25 16 20 17 26 E&WRidings 9 6 1 26 0 1 10 10 0 London 8 5 7 2 22 18 2 4 10 Midlands 9 12 24 6 1 4 16 6 1 Northern 8 10 9 10 20 3 3 8 15 North Midlands
7 3 6 15 1 13 8 7 5
Northwestern 11 11 3 8 1 3 19 11 3 Southeastern 7 11 5 4 1 8 2 3 2 Southern 8 8 6 4 14 5 12 8 18 Southwestern 8 9 6 6 1 3 1 9 19 Scotland 10 9 10 5 14 24 3 10 0 Wales 5 5 21 5 0 1 1 7 1
International Consortium for BP GWAS
International Consortium for Blood Pressure Genome-Wide Association Studies. Nature 2011
200,000 Individuals: 16 Novel Loci
International Consortium for Blood Pressure Genome-Wide Association Studies. Nature 2011