The main list of sources we used for the ‘Genetics: risk or destiny?’ graphic is available on Google Sheets.
The notes below expand on some of the points raised by these data and link to additional resources.
Huntington’s disease in the UK population
Between 1990 and 2010, the average prevalence of Huntington’s disease was 10.0 per 100,000 people (1 in 10,000).
Note this is a prevalence statistic for the disease (based on patient diagnosis), not the variants in the HTT gene that cause it. A normal HTT gene contains between 10 and 35 CAG repeats. A mutated gene is therefore one that contains more than 35 repeats. However, the disease is only certain to develop in individuals with a gene with 40 or more CAG repeats. If someone has a mutated gene with 36–39 CAG repeats, they might or might not develop the disease.
In this graphic, therefore, we’re referring to gene variants with 40 or more repeats. The odds of developing the disease are 1 in 1 with the variant of 40 or more repeats and 0 in 1 with 35 repeats or fewer. For simplicity we have not included 36–39 repeat cases in the graphic, but we can assume that some 36–39 repeat cases will be included in the overall prevalence figure.
Breast cancer in the female UK population
It’s estimated that variants in the BRCA1 and BRCA2 genes are carried by “0.11% and 0.12% of women in the general population”, respectively.
Note that it’s possible to have mutations in both genes. Thus, there could be an overlap across these two figures, reducing the combined total. However, we haven’t identified any statistics on this to date.
Data from 2003 indicate a 65 per cent average cumulative risk of breast cancer by the age of 70 in BRCA1-mutation carriers. The corresponding estimates for BRCA2 were 45 per cent. As the graphic indicates, the general population figure indicates lifetime risk.
Factors that increase your chance of getting a disease
Here we’ve defined genetic risk as mean heritability (h2) drawn from several studies, weighted by sample size.
For Huntington’s disease we’re referring to the risk of developing the disease for someone who is carrying a variant of the HTT gene with 40 or more CAG repeats.
For coronary heart disease (41 per cent) and lung cancer (10 per cent), we’re referring to the weighted means of all the heritability estimates drawn from research papers (see ‘Heritability calcs’ in the Google Sheet).
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. An affected person usually inherits the altered gene from one affected parent, and a normal version from the other. In rare cases, an individual with Huntington’s disease does not have a parent with the disorder.
Adult-onset Huntington’s disease, the most common form of this disorder, usually appears in a person’s 30s or 40s. See also Table 3 in this 2013 research paper.
Coronary heart disease
“Genetic or lifestyle factors cause plaque to build up in your arteries as you age. By the time you’re middle-aged or older, enough plaque has built up to cause signs or symptoms. In men, the risk for CHD [coronary heart disease] increases after age 45. In women, the risk for CHD increases after age 55.” This source – The US National Heart, Lung and Blood Institute – also notes many of the other risk factors discussed below.
“Other risk factors for developing atherosclerosis include: [...] being obese.” – NHS Choices
The risk of developing atherosclerosis is significantly increased by high blood pressure and diabetes.
See the section ‘How stress causes cardiovascular disease’ by the World Heart Federation.
Drinking more than the recommended amount of alcohol can cause abnormal heart rhythms, high blood pressure and damage to the heart muscle (and other conditions such as stroke, liver problems and some cancers).
“Your risk of developing atherosclerosis is significantly increased if you: [...] do not take regular exercise.” – NHS Choices
“Your risk of developing atherosclerosis is significantly increased if you: [...] smoke.” – NHS Choices
Exposure to particulate matter air pollution from car emissions, power plants, and other sources is an environmental risk factor for coronary heart disease.
“If you have a first degree relative with lung cancer your risk of lung cancer is increased by 50%. The risk is even greater if a brother or sister has lung cancer, rather than a parent. This risk is regardless of whether or not you smoke. But families of smokers might be exposed to cigarette smoke and so have an increased risk of lung cancer whether they have inherited a faulty gene or not.” – Cancer Research UK
“Smoking cigarettes is the single biggest risk factor for lung cancer.” – NHS Choices
“Research also suggests that being exposed to large amounts of diesel fumes for many years may increase your risk of developing lung cancer by up to 50%. One study has shown that your risk of developing lung cancer increases by about a third if you live in an area with high levels of nitrogen oxide gases (mostly produced by cars and other vehicles).” – NHS Choices
UK deaths from coronary heart disease
The figure in the graphic – 13 per cent – is based on the 2013 death registration table, from the UK Office of National Statistics. In 2013 there were 506,790 deaths (males and females), of which 63,872 (12.6 per cent) were caused by ischaemic heart diseases (aka coronary heart disease).
Factors affecting the risk of developing coronary heart disease
The full name of the variant is MTHFR 677 TT.
￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼“Individuals with the MTHFR 677 TT genotype had a 16% (OR, 1.16; 95% confidence interval [CI], 1.05-1.28) higher odds of CHD compared with individuals with the CC genotype.” – 2002 meta-analysis published in JAMA
Note that this variant in the MTHFR gene is just one of many associated with an increased risk of coronary heart disease. A 2014 paper discusses 50 genetic risk variants, while the Wellcome Trust Sanger Institute suggested in 2012 an even greater number (46 genetic regions associated with the disease, with a further 104 variants suspected).
“If you smoke, you increase your risk of developing heart disease by 24%.” – NHS Choices
“The confounder-adjusted HR [hazard ratio] of obesity versus normal weight was 1.69 (1.58–1.81) for coronary heart disease and 1.47 (1.36–1.59) for stroke.” – 2014 paper published in the Lancet
Symptoms of some diseases can be reduced by behaviour
“PKU is treated with a special low-protein diet... The phenylalanine in your body comes from protein in your diet, particularly high-protein foods, such as: meat, fish, eggs, cheese, milk.” – NHS Choices
“Any products containing aspartame should be avoided.” – MedlinePlus
“Under ACE (additive genetic, common, and unshared environmental factors) models, with CD population prevalences of 1/91 and 1/1000, heritability estimates were 87% and 57%, respectively.” – 2006 Gut paper
“In the case of coeliac disease, your immune system mistakes one of the substances that makes up gluten, called gliadin, as a threat to the body.” – NHS Choices
“Coeliac disease is usually treated by simply excluding foods that contain gluten from your diet.” – this NHS Choices page also has a list of specific foods.
Some gene variants can be good for you
“The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers.” – 2014 NEJM paper
“Collectively, carriers of protein-truncating variants had 65% reduced [type 2 diabetes] risk.” – Nature Genetics 2014
This study of Swedes and Finns identified 12 different variants in the SLC30A8 gene, all of which produced shorter versions of the protein and reduced the risk of type 2 diabetes.
“People with two copies of the CCR5 delta32 gene (inherited from both parents) are virtually immune to HIV infection…It's not an airtight guarantee of never getting AIDS. Some unusual types of HIV can use other proteins for entering cells. Rarely, there have been people who have two mutant CCR5 genes who have died from AIDS.” – The Tech
So the reduction is close to 100 per cent, but it isn’t absolute. Furthermore, a person needs to have the delta32 variant in both copies of their CCR5 gene for this level of protection. The protective efficacy of a single gene alone is much lower: “Quantitative studies have concluded that heterozygous carriers of Δ32 in the past had a fitness advantage of at least 5% and possibly as high as 35%.”
Likelihood of carrying any of these variants
The APOC3 study noted above looked at Americans of European or African ancestry, and the SLC30A8 study looked at individuals from Sweden and Finland. The CCR5-delta 32 mutation is found in people of European descent only, so the global prevalence is far smaller than 1 per cent.