My experiences with invisible illnesses have undoubtedly altered my perspective in life, especially in my approach to the courses I take. As a college student majoring in biology, I had the opportunity to take a course in Classical Genetics this past semester. Throughout the class, I learned about new technologies that are relevant to current research in genetics. In internalizing this information, I realized that these are some of the techniques that physicians and scientists use to elucidate the nature of many invisible illnesses.
In order to make strides in chronic condition treatment options, we may come across opportunities to become a part of translational research efforts. If the cause of a condition is yet to be determined, genetic studies could be critical for coming to a more precise conclusion. Although it is unlikely that this kind of approach would uncover a purely genetic explanation for a disease that has not already been determined, a person could have a genetic predisposition to the disease. This means that a person is more susceptible to developing a certain condition because of certain variations in their genetic makeup. This is complicated by the fact that diseases are typically multifactorial, meaning that other genetic, lifestyle, and environmental factors play a role in disease development. Nonetheless, it is important to study the genetic factors of invisible illnesses as a means of preventing disease development and creating targeted therapeutics. Thus, I want to share the basic science behind Genome-Wide Association Studies (also known as GWA Studies) and how they can be applied to the study of invisible illnesses.
Here are some terms that are helpful for understanding the background of GWAS:
Genes: the units of heredity; they serve as the blueprints for the body and give rise to traits.
Alleles: different sequence versions of the same gene. For example, there are three alleles for blood type - A, B, and O. Each person carries two alleles for a gene, and those alleles could be the same (i.e. in a person with blood type O) or different (i.e. in a person with blood type AB).
DNA: short for deoxyribonucleic acid, it is the molecular basis for genes. It stores information as a code for life in the form of four differentially repeating chemical bases, adenine (A), guanine (G), cytosine (C), and thymine (T). DNA is doubled stranded, so a base on one strand pairs with a base on the other strand (A and T always pair together; G and C always pair together).
Chromosome: a strand of DNA that is tightly packaged to fit into a cell's nucleus. Each chromosome contains many genes, as well as specific proteins to maintain its structure.
Human genome: the complete DNA sequence that exists in (most) cells. It is made up of 23 pairs of chromosomes, altogether comprising around 3 billion DNA base pairs.
It is estimated that the genetic variation between any two individuals is .1% - only 1 in every 1,000 base pairs is different. These small differences in the DNA sequence are usually single nucleotide polymorphisms (commonly known as SNPs, pronounced "snips"), and each one accounts for one base-pair difference in an allele. Due to the fact that human genomes are quite similar to each other, scientists have been able to map the genome to pinpoint where these SNPs occur. A Genome-Wide Association Study takes advantage of this information by analyzing the SNPs of certain patient populations, potentially unveiling a link between certain SNPs and disease prevalence.
Technically speaking, a GWA study utilizes DNA sequencing technology to identify hundreds or thousands of SNPs for each individual. In order to establish the existence of a true correlation between a genetic marker and a condition, a GWA study necessitates the enrollment of thousands of people for a study, including a group of patients that meets the diagnostic criteria for the condition being investigated and a group of unaffected patients to act as a control. SNPs that are associated with the disease cases at an appropriate statistical threshold are then genotyped in a second independent sample of cases and controls to establish which of the associations from the primary scan are robust.
GWA studies are not limited to risk prediction and screening. They can allow scientists to better classify diseases into subtypes so that more personalized treatment options can emerge. Additionally, GWA studies can be utilized to provide information regarding gene-drug interactions for drug development fields. An example of success in this area is the finding of a strong association between SLCO1B1 variants with myopathy, related to simvastatin therapy, which is used to lower blood cholesterol levels by reducing cholesterol production in the liver. Myopathy occurs in 1–5% of patients treated with this class of drugs and is characterized by muscle pain, weakness, and elevated muscle enzyme levels. Dosing guidelines have been issued by the Clinical Pharmacogenomics Implementation Consortium for managing simvastatin-induced myopathy risk in the context of SLCO1B1 genotyping.
This approach has already identified SNPs related to several complex conditions including diabetes, heart abnormalities, Parkinson's disease, Crohn's disease, and several types of cancer. When I was learning about GWA studies in my genetics course, I thought that perhaps it could be used to provide further insights into invisible illnesses that are not fully understood. Approximately 80% of the over 7,000 rare diseases that have been discovered are genetic in origin. Those can be considered monogenic diseases (as caused by a singular genetic mutation), whereas more common diseases are multigenic, in which certain alleles contribute around 2-50% to disease risk.
I hope that researchers can continue to recognize the benefits of Genome-Wide Association Studies for invisible illnesses and employ this methodology for more conditions. I think that it is important as the medical field transitions towards precision-based medicine that we attempt to increase knowledge about common and rare diseases alike. This is why The Invizibles strives to raise awareness and funds for invisible illness patients and research, respectively.
How can you get involved with The Invizibles?
You can share your story! I am starting a special series as part of the weekly blogs in which I interview others that have struggled with an invisible illness. If you are interested in sharing your experience, please email firstname.lastname@example.org.
I am also holding a printed-collage fundraiser to raise money for invisible illness research, Custom-made collages can be printed and shipped to your doorstep, and 100% of the proceeds will go towards scientific research funding. Fill out this form and you will be contacted for confirmation: https://forms.gle/faEuEiuzZ2vL4XUS7.
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Invisible illnesses present hidden challenges; let's uncover and solve them together.