The Genomic Revolution Continues: Genetic Basics and Types of Genetic Tests
By Dr. Phil Smalley MD, FRCPC
This is part two of a continuing series. Be sure to check out part one here.
For the insurance and employee benefits professional to understand the different types of genetic tests, you first need to know the vocabulary.
- We have 23 pairs of chromosomes (one set of 23 from each parent) containing 6+ billion nucleotide chemical bases (G, A, T, and C) and about 20,000 functional genes (1)
- Genes make RNA that in turn make proteins which perform important functions in the body to keep us healthy
- Germline is the set of genes you were born with that are in almost every cell of your body
- Gene mutations or variances can result in the formation of a protein with altered function that can cause disease or cancer
- As researchers find new mutations and new gene-disease associations, the interpretation of your genome report will evolve over time
It has been shown that even though our germline DNA remains fairly constant throughout our lives, some changes still occur with aging. For example, cells can lose the Y sex chromosome with aging and this is associated with cancer, Alzheimer’s Disease and other illnesses. (2) Also, the ends of our chromosomes called telomeres, shorten over time and this is associated with increased mortality. (3)
Various adverse environmental factors (such as smoking, sun exposure, viruses, chemical exposure, etc) can also cause new mutations in our DNA in various organs. The body tries to repair these mutations when they occur, but if this repair of our DNA fails, these mutations can lead to cancer.
Genes are not Fate
- All humans are about 99.5 percent the same genetically (4)
- Twin studies show that about 25 percent to 50 percent of observed differences in morbidity and mortality from person to person is due to genetics. (5, 6) Environmental and lifestyle factors make up the rest of the variance
- Between 1.2 percent to 3.4 percent of the healthy population are walking around with incidental actionable genetic mutations that if known, could allow your doctor to take measures to prevent disease (7)
- You can still get a disease even though your genetic test is normal with no reported genetic mutations because not all genetic causes of diseases are yet known and because of environmental factors causing disease
- Knowing your genetics can help motivate you to adopt a healthier lifestyle to lower your disease risk
Most of us are carrying some mutations that put us at an increased risk to develop some disease. But in many circumstances, this risk can be mitigated with lifestyle changes along with preventative medical treatments and early screening. A 2016 study by Khera shows that people with a high genetic risk score for heart disease have about double the rate of heart disease compared to those with a low genetic risk score. But this excess genetic risk is lowered by 46 percent if the person has a favorable lifestyle. (8) Even in Alzheimer’s Disease, those carrying the increased risk ApoE4 genetic trait can mitigate at least some of their risk by altering their diet and adopting a healthy lifestyle. (9,10,11)
Some mutations actually protect us from getting diseases. For example, a mutation in the CCR5 gene that occurs in 1 percent – 10 percent of some populations, makes these carriers resistant to the HIV/AIDS virus. (12) The genetic mutation that causes Sickle Cell Disease trait infers some resistance to malaria. (13) A review by Dose in 2016 reports that the ApoE4 genetic variant that is associated with an increased risk of Alzheimer’s Disease is also associated with resistance to various infections. Also, women carrying ApoE4 are at lower risk of spontaneous abortions and still births. (9)
Types of Genetic Tests
There are many different types of genetic tests that are already being incorporated into employee benefits and in insurance products. (Figure 1) The different genetic tests vary significantly in price, availability, validity, utility, and speed with which a result is reported back to the patient’s doctor.
Whole Genome Sequencing (WGS) is the most comprehensive test as it decodes the vast majority of your DNA looking for mutations or variances.
- Predicts risk of developing diseases in the future. Magnitude of the risk depends on other factors such as age, gender, ethnicity, family history, personal history, etc
- Predicts effectiveness of medications and determines if you are genetically susceptible to serious drug side effects. This is called pharmacogenomic testing (PGx)
- Can determine if you are carrying abnormal genes that you could pass along to your child
- Can help individualize diet and response to exercise. This is called nutrigenomics
- Since WGS decodes most of your DNA, this permits lifelong ongoing reevaluation as new discoveries occur without having to repeat the test
Some genetic tests only sequence the protein producing genes that make up 1 percent of our DNA, which is called Whole Exome Sequencing (WES).
The cheapest form of genetic test is called a genome wide association study (GWAS), an example being 23andMe’s direct to consumer genetic testing service that outputs a genotype. GWAS testing looks only at a small fraction (< 0.1 percent) of our DNA for genetic variants called ‘single nucleotide polymorphisms’ or SNPs. Population studies show that certain SNPs are associated with an increased risk of developing a particular disease or drug side effect. These tests also report about ancestry, genetic traits, drug side effect susceptibility and information about disease carrier status that might be transferable to future offspring. Unlike sequencing your genome, when there’s a new discovery, this GWAS test would need to be repeated to reassess your risk profile.
Genetic testing is also available looking only for specific genetic mutations to help a doctor make a medical diagnosis or determine disease severity or prognosis.
Genetic tests can be done on blood or saliva to look at your germline for either WGS, WES, GWAS, or PGx assessment. Or we can test for specific genetic mutations or alterations in cancer tissue. Finding mutations in cancer cells can lead to new targeted forms of cancer therapy that can extend quality and quantity of life, improving employee health and lowering mortality for an insurer which can add significantly to the profitability bottom line.
In next month’s October article, we will discuss more about the accuracy of these genetic tests and how useful are the results as it relates to cancer genomic profiling, pharmacogenomics, and whole genome sequencing. We will show that even though we are slightly ahead of the clinical medicine curve, incorporating these genetic tests into employee benefits and insurance products can improve quality and quantity of life and decrease health care costs.
I invite you to answer this anonymous one question online survey and see what others think about genetic testing. Also, post your comments and opinions in the comments section below as we start this open discussion.
All content in this article was created for informational purposes only. The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician, genetic counsellor or other qualified health provider with any questions you may have regarding a medical condition or testing. Never disregard professional medical advice or delay in seeking it because of something you have read in this article. Reliance on any information provided in this article is solely at your own risk.
About the Author
Dr. Phil Smalley is an Internal Medicine specialist with 27 years of experience in insurance medicine. He recently retired from his position as Senior Vice President and Global Chief Medical Officer for RGA International Corporation. Dr. Smalley received his medical degree from the University of Toronto, Canada. He is a Fellow of the Royal College of Physicians and Surgeons of Canada and Past President of the Canadian Life Insurance Medical Officers Association. Dr. Smalley was also Managing Director of the Longer Life Foundation, the not-for-profit research partnership between RGA and Washington University School of Medicine. Dr. Smalley currently lives in Toronto consulting for the insurance industry and is Chief Medical Director for Wamberg Genomic Advisors.
About Wamberg Genomic Advisors
Wamberg Genomic Advisors is your partner in the Genomic Revolution. Our mission to make genomic testing readily available at prices everyone can afford. Our focus is on delivering genomic products and services to employers and their employees via their trusted benefit brokers and policyholders of life insurance companies. To discover more about WGA and the future of genomics, visit wamberggenomic.com.
- Ezkurdia, I et al. Multiple evidence strands suggest that there may be as few as 19,000 human protein-coding genes. Hum Mol Genet. 2014 Nov 15;23(22):5866-78
- Forsberg LA. Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men. Hum Genet. 2017 May;136(5):657-663
- Steenstrup, T et al. Telomeres and the natural lifespan limit in humans. Aging (Albany NY). 2017 Apr;9(4):1130-1142
- Levy, S et al. The diploid genome sequence of an individual human. PLoS Biol. 2007 Sep 4;5(10):e254
- Christensen, K and Vaupel, JW. Determinants of longevity: genetic, environmental and medical factors. J. Intern Med. 1996 Dec;240(6):333-41.
- Polderman, TJ et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet. 2015 Jul;47(7):702-9
- Dorschner, MO. Actionable, pathogenic incidental findings in 1,000 participants’ exomes. Am J Hum Genet. 2013 Oct 3;93(4):631-40
- Khera, AV et al. Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. New Engl J Med. 2016 Dec 15;375(24):2349-2358
- Dose, J. et al. APOE genotype and stress response – a mini review. Lipids Health Dis. 2016 Jul 25;15:121
- Villeneuve, S et al. The potential applications of Apolipoprotein E in personalized medicine. Front Aging Neurosci. 2014 Jul 8;6:154
- Kivipelto, M et al. Apolipoprotein E epsilon4 magnifies lifestyle risks for dementia: a population-based study. J Cell Mol Med. 2008 Dec;12(6B):2762-71
- Rugeles, MT et al. Mechanisms of human natural resistance to HIV: a summary of ten years of research in the Colombian population. Biomedica. 2011 Jun;31(2):269-80
- Luzzatto L. Sickle cell anaemia and malaria. Mediterr J Hematol Infect Dis. 2012;4(1):e2012065