Whole Genome Sequencing: What It Can and Cannot Tell You

Why this matters

Genetic testing is easier to access than ever, but the tests on offer vary a great deal. Understanding what whole genome sequencing reads, and what it does not tell you, helps you decide whether it suits you and how to use the results sensibly.

What whole genome sequencing reads

DNA is the set of instructions inside your cells that tells the body how to grow and work, written in a code of four chemical letters. Your genome is your complete set of DNA, around three billion letters. Whole genome sequencing reads almost all of them. Each part is read many times to improve accuracy; 30x coverage means each position is read about thirty times on average.

Ancestry-style tests work differently. They use a genotyping chip, a test that checks a selection of known positions, typically several hundred thousand, which is a small fraction of the genome. That is enough for ancestry and some traits, but it misses much of the detail sequencing can capture.

What it can tell you about immune health

Genes are sections of DNA that each carry the instructions for one part of how the body works. The HLA genes help the immune system tell the body's own cells apart from threats such as germs, and certain versions (HLA types) are strongly linked with particular conditions. HLA-B27, for example, is linked with ankylosing spondylitis, a type of inflammatory arthritis that mainly affects the spine, and HLA-DQ2 and DQ8 are linked with coeliac disease. Not carrying DQ2 or DQ8 makes coeliac disease very unlikely, while carrying them is common and does not mean you will develop it.

Sequencing can also show variants, small differences in the DNA code between people, linked with inherited risk across many conditions, and variants that help explain why some blood markers, such as cholesterol, sit higher or lower in some people.

What it can tell you about medicines

Some genes affect how quickly the body processes certain medicines. A well-known example is the TPMT gene, which affects how quickly the body breaks down azathioprine, a medicine that calms the immune system and is used in several immune conditions. This kind of information is something to discuss with your clinician; it should never be used to change a medicine on your own.

What it cannot tell you

A genetic variant tells you about inherited likelihood, not about what is happening in your body now. Most autoimmune conditions involve many genes, each with a small effect, together with environmental factors such as infections, smoking and hormones. Many people with risk variants never develop a condition, and many people with a condition carry no well-known risk variant.

Consumer genome sequencing is not a diagnostic test (a test that confirms whether you have a condition) and is not the same as clinical genetic testing arranged through the NHS. If a condition runs strongly in your family, your GP can advise whether an NHS genetics referral is appropriate.

What you could do

Genetic results are most useful as background context that you return to over time.

• Decide what you want to learn before you test, and how you would feel about unexpected findings
• Read results as likelihood, not certainty, and combine them with symptoms and blood results
• Share anything relevant to medicines with your GP or specialist before making any changes

This article is for general information only and is not a substitute for medical advice. If you are worried about your health or your results, speak to your GP or specialist team. In an emergency, call 999 or go to A&E.

References:

NHS England, 'Genomics' https://www.england.nhs.uk/genomics/

Coeliac UK, 'Diagnosis' https://coeliac.org.uk/healthcare-professionals/diagnosis