The risk of cardiovascular disease is determined by the complex interplay between an individual's genetic make-up, lifestyle, and the environment. The researchers in this observational, cross-sectional, recall-by-genotype study are investigating two potential genetic risk factors; the SWAP70 gene is thought to play a role in the immune response modulating cardiovascular disease risk and the GMPR gene plays a role in red blood cell formation. The investigators hope to identify and characterise distinct molecular and cellular mechanisms underlying candidate functional variants identified in genetic studies of cardiovascular and immune-related human traits and diseases.

Healthy volunteers who are part of the NIHR BioResource and have already been genotyped will be invited to the study based on their genotype of the candidate functional variants of interest. Volunteers will attend a single study visit, during which they will complete procedures including a medical, demographic and lifestyle factors questionnaire; height, weight and body fat assessments; in addition to blood pressure/heart rate measurements. A minimally invasive procedure of a venepuncture will be performed to assess the primary objectives of the study.

The obtained data may (1) improve understanding of biological and disease mechanisms; (2) identify potential drug targets; and (3) improve insight into the therapeutic potential and limitations of existing and emerging therapies.

This study is funded by the UK Medical Research Council, British Heart Foundation and NIHR Cambridge Biomedical Research Centre.

Inclusion Criteria:

• Have consented to be part of the NIHR BioResource;
• Are aged 18 years and above;
• Have given written informed consent to participate in the GENBIO study;
• Are carriers or non-carriers of the candidate functional genetic variant(s) of interest.

Exclusion Criteria:

Have a chronic disease, including cardiovascular diseases, autoimmune diseases and cancer.

Additional exclusion criteria to be applied at the discretion/opinion of the CI/collaborator, based on the population of available volunteers for recall and the genetic variant of interest (e.g. allele frequency):

• Have a biological first-degree relatives (parents, brothers, sisters or children) who are suffering or have suffered from a disease/condition in the opinion of the CI/collaborator that, from a genetic standpoint, may affect the study validity;
• Are current regular smokers. Regular ex-smokers are suitable if they stopped smoking >10 years ago (regular defined as 1 pack year in both instances);
• Have ≥3 alcoholic drinks per day;
• Have a diagnosis of hypertension, or history of consistently high blood pressure readings, e.g. >140/90 mmHg;
• Have a diagnosis of hypercholesterolemia, or history of consistently high cholesterol levels, e.g. total cholesterol level >6 mmol/l;
• Are obese (i.e. BMI >30);
• Are unwilling to fast and not to consume products containing alcohol or caffeine 12 hours prior to procedures.

The study will only recruit healthy volunteers who have previously consented to being contacted for future studies by the NIHR Cambridge BioResource, which is a panel of around 20,000 volunteers, both with and without health conditions, who are willing to be approached to participate in research studies investigating the links between genes, the environment, health and disease. Volunteers who join the NIHR BioResource have donated their DNA via a blood or saliva sample that is used together with other information, such as sex and ethnicity, to match them to specific research studies. Participants for this study are identified by having the appropriate genetic sequence in one of the two genetic loci we are investigating (SWAP70, GMPR).

Participant identifiable information is securely held, with restricted access, by the NIHR BioResource. Members of the research team carrying out the procedures will not be able to request the link to decode this information. Only the minimum required participant identifiable information (name and contact details) will be provided to the research team for the purpose of arranging study visits and completing the informed consent process. All research personnel will be sufficiently blinded of the genotype status of the healthy volunteers. All delegated research personnel that is responsible to conduct the data/statistical analysis will only analyse data that is anonymised of any patient identifiable data.