BBMRI-NL is het samenwerkingsverband tussen biobanken in Nederland. BBMRI-NL is opgezet omdat voor het beantwoorden van belangrijke vragen onderlinge samenwerking tussen biobanken essentieel is. BBMRI-NL is het Nederlandse knooppunt binnen het Europese Biobanking and Biomolecular Resources Research Infrastructure (
BBMRI).
Hieronder treft u een samenvatting (Engels) van de participatie van SMART aan BBMRI.
No.: 44
Title: DNA isolation in the SMART (Second Manifestation ARTerial disease) cohort
Principal investigator(s): Prof.dr. Y. van der Graaf, Prof.Dr.A.Algra
Collaborators / team members: P.I.W. de Bakker, F.W. Asselbergs
Summary: The SMART study is a collaborative effort throughout the UMC Utrecht involving investigators and clinicians from all the departments involved in cardiovascular care and research (www.vaatcentrum.nl). The main objectives of the SMART study are to determine factors that influence the occurrence of future events in patients at high risk of cardiovascular disease. Over 10.000 patients were included since 1996 and followed 6-monthly for cardiovascular events and interventions.
Email address: y.vandergraaf@umcutrecht.nl
Website: www.vaatcentrum.nl
Institutes involved: UMC Utrecht
Biobanks involved: SMART (Second Manifestation ARTerial disease)
International collaboration(s): e.g. University College London, CHARGE consortium, HaemGen consortium, International Stroke Genetics Consortium, International SCD Consortium, International QRS Voltage Genetics Consortium, QT-International Genetics Consortium.
No. of subjects / samples in project: 5000
Start date and (anticipated) end date: August 2010
Results so far: DNA isolation has been performed in 5000 subjects and are plated for wet-lab genotyping. In addition, normalized DNA is available in aliquots for future high-throughput genotyping using commercial arrays. During the first months after DNA isolation, several genotyping projects have already been performed. Wet-lab genotyping for single nucleotide polymorphism (SNP) analysis was carried out by KBiosciences, Hertfordshire, UK. (www.kbioscience.co.uk) using their proprietary KASPar PCR technique. At time of this writing, several manuscripts have been prepared using genotype data from SMART. Hereby the titles of the submitted manuscripts:
- Genetic approach to interrogating the causal role of secretary phospholipase A2-IIa in primary and recurrent coronary heart disease in 66,298 individuals with 14,123 events. Prof. P. Talmud, University college London.
- The interleukin-6 receptor as a potential target for coronary heart disease prevention: evaluation using Mendelian randomization. Dr. JP Casas, University college London.
- Association of variants at 1q24.3 with expansive vascular remodelling and risk of abdominal aortic aneurysm. Prof. S.E. Humphries, University College London.
- Next to the abovementioned papers, approximately 10 manuscripts are in preparation and will be submitted for publication in the next 6 months. Hereby a short summary of the ongoing projects:
- Can genomic profiling improve existing population based screening program– Abdominal Aortic Aneurysm (AAA) as an exemplar. Collaboration: Prof. S.E. Humphries, University College London.
- Evaluation of a CAD-related genetic risk burden score in different vascular beds.
- Common variants in HMGCR are proxies for the mechanism-based actions of statins: a Mendelian randomisation drug target validation study. Collaboration: Prof. A. Hingorani, University College London.
- Effects of statin therapy on body mass index, markers of glycaemic control, and risk of diabetes are likely to be mechanism-based: investigation using Mendelian randomisation. Collaboration: Prof. A. Hingorani, University College London.
- Common variant of aldosterone synthase gene as model for the role of aldosterone in atherosclerosis using Mendelian randomization. University Medical Center Groningen, University Medical Center Groningen, Prof. W. Maerz, LURIC, Prof. V. Ramachandran, Framingham Heart Study.
- ADH1B (rs1229984) Alcohol & Cardiovascular Biomarkers. Collaboration: Dr. JP Casas, University college London.
Finally, SMART investigators are active members of several international consortia performing multiple large genome-wide meta-analysis. Replication of novel loci detected by these consortia will be performed within SMART. At this moment, genotyping for replication purposes is performed for the following traits:
- QRS-voltage. Collaboration: International QRS Voltage Genetics Consortium including University Medical Center Groningen and University Medical Center Utrecht.
- Hemoglobin/Packed Cell Volume. Collaboration: HaemGen including University Medical Center Groningen and University Medical Center Utrecht.
- Stroke. Collaboration: International Stroke Genetics Consortium.
- White matter hyperintensity/lesions. Collaboration: International Stroke Genetics Consortium.
- Sudden Death. Collaboration: International SCD Consortium including Academic Medical Center Amsterdam.
- QT duration. Collaboration: QT-International Genetics Consortium.