B655 - Replication studies of hypertension genes - 29/05/2008

B number: 
Principal applicant name: 
Prof Mark Caulfield (Barts and London School of Medicine, UK)
Patricia Munroe (Not used 0, Not used 0), Martin Farrall (Not used 0, Not used 0), David Clayton (Not used 0, Not used 0), Maurice Brown (Not used 0, Not used 0), Anna Dominiczak (Not used 0, Not used 0), John Connell (Not used 0, Not used 0), Nilesh Samani (Not used 0, Not used 0), Mark Lathrop (Not used 0, Not used 0), John Webster (Not used 0, Not used 0)
Title of project: 
Replication studies of hypertension genes
Proposal summary: 


There are over 1 billion people with high blood pressure worldwide and simulations by the World Health Organisation suggest this will rise to 1.5 billion by 2020 [1]. It is estimated that blood pressure played an important part in 50% of the 16.7M cardiovascular deaths worldwide [1, 2]. In spite of the availability of multiple different therapeutic strategies, public health data from western economies shows hypertension remains poorly controlled.

The Wellcome Trust Case Control Consortium and replication of signals

In the first phase of WTCCC 2000 hypertensives from the BRIGHT Study were subjected to a genomewide scan using the Affymetrix 500 chip and compared with 3000 common controls. We found comparable numbers and distribution of suggestive association signals in the range P less than 10-4 to 10-7 compared with the 6 other diseases investigated [3]. We are actively pursuing the most promising signals from WTCCC1 and parrallel candidate gene studies in extended replication resources and have waited to approach ALSPAC until we had evidence that some of these signals had survived initial replication with blood pressure and hypertension with decreasing P values. We have also found association of SLC2A9 SNPS with urate and a borderline association with blood pressure. In a second candidate gene we have found a developmental gene that influences nephron number to relate to blood pressure. ALSPAC represents and ideal resource for evaluation of these putative associations.

Reasons for approaching ALSPAC now.

Our reasons for approaching ALSPAC childrens DNA bank now is to investigate association of these variants with early life blood pressure ( at all time points you have these measures) and flow mediated dilatation as a measure of endothelial function (at all time points). In at least 2 cases the genes are implicated in nephron development which makes investigation of early life association of blood pressure valuable. One of these genes might also be involved in control of birthweight ( testing association with measures of birth weight and anthropometry might be interesting). If there was access to renal function measures such as eGFR or urea and creatinine we would also be interested in these but we think from what we can tell these may not be available. We would be happy to receive advice on any other phenotypes you think we should test.

Genotyping at KBioscience and funding.

We provide below a list of SNPs for genotyping on fast-turn around at K Bioscience and will fund this work from our MRC Programme.

Date proposal received: 
Thursday, 29 May, 2008
Date proposal approved: 
Thursday, 29 May, 2008
Primary keyword: