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Brain Inflammation Blog #3: Largest Disease-Specific Genome Test Fails to Find Actionable Associations in Migraine, Reinforcing the Perspective that Genomic Testing is Barking up the Wrong Tree
PDF of articles with additional information
Dr Alex Vasquez, 29 Sep 2016
Note: Dr Vasquez's expertise on the topics of fibromyalgia, dysbiosis, nutrition, functional medicine, clinical medicine, and microbiome/dysbiosis is demonstrated by the following publications (and more) plus numerous international post-graduate presentations since 2001:
Translating Microbiome (Microbiota) and Dysbiosis Research into Clinical Practice: The 20-Year Development of a Structured Approach that Gives Actionable Form to Intellectual Concepts. International Journal of Human Nutrition and Functional Medicine 2015 Jun PDF
Mitochondrial Medicine Arrives to Prime Time in Clinical Care: Nutritional Biochemistry and Mitochondrial Hyperpermeability (“Leaky Mitochondria”) Meet Disease Pathogenesis and Clinical Interventions. Integr Med 2014 Aug
Dr V's perspective on new research recently summarized in the journal Genome Medicine: I readily admit that while I appreciate the potential promise of so-called genomic "precision medicine", I am also of the opinion that the rabid over-enthusiasm for this technology is fueled by the profiteering motives of 1) data compilation and distribution, 2) maintaining current status quo of drug dependency by a) associating specific genes with specific drugs, and b) promoting inertia while the medical community sits on its hands awaiting the never-quite-ready delivery of the promise of genomic/precision medicine, which although valid in premise in rare instances is largely ridiculously reductionistic in its basis and attempt to prove that diseases are based on genetic defects in need of pharmacologic repair. Also, with my having reviewed the research and pathophysiology of migraine for the past 17 years and via the publication of many articles and book chapters, I am far from convinced that a somatic gene defect is going to be found that then translates into a medical miracle that alleviates this condition because 1) many non-genetic contributors have already been identified, and 2) the mitochondrial model of the disease as I have summarized in my recent books such as Brain Inflammation / Pain Revolution, excerpted from Inflammation Mastery 4th Edition is the most durable and complete model of the disease ever published, elegantly simple though it may be. My main thesis is that migraine is a disorder of mitochondrial function with secondary glial activation, neuron dysfunction, and tertiary pain; the failing of the largest GWA* ever conducted in the history of medicine to find any actionable associations reinforces the perspective that migraine is a phenotypic functional disorder and not a genotropic disorder, at least not as far as the nuclear genome is considered.
When a large study of a common disease finds virtually nothing, a reasonable conclusion is that the researchers are using a faulty paradigm of the disease: As "the most prevalent and disabling neurological disorder", migraine provides a large subject pool for research (and drug sales); this is a common disorder, the opposite of an orphan disease. Recently, the largest disease-specific *genome-wide association (GWA) study ever conducted in the history of medical science was completed, and it found nothing actionable that could be translated into clinical care.
"The most recently published migraine study, comprising data from 375,000 individuals, represents the largest published GWA study of any specific disease. ... Although the advances in GWA studies represent major progress, it is perhaps too early to say whether, in the short term, the common variant loci found could directly help to influence patient care." Gormley et al. Migraine genetics: from genome-wide association studies to translational insights. Genome Medicine 2016; 8:86 DOI: 10.1186/s13073-016-0346-4
Migraine is a multicomponent functional disorder, not a genetic disease: The model of migraine that in my opinion provides the most complete and facile understanding of the condition is as follows: mitochondrial dysfunction causes metabolic fragility and increased ROS and inflammation, thereby promoting both glial activation and neocortical hyperexcitability; the vascular phenomena are secondary to the metabolic collapse involving the totality of the parenchyma as well as the ROS-induced and inflammation-induced changes in vasodilation/vasoconstriction, which create the vicious cycle of metabolic collapse that I have termed "pain revolution", depicted as a circle that interconnects mitochondrial fatigue, brain excitation, and glial inflammation.
FOR CLARITY: Chapter 5.1b from Inflammation Mastery 4th Edition was published separately as
Pain Revolution in color and later as
Brain Inflammation in discounted grayscale; the digital versions are identical.
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Overview (Part 1) of the Functional Inflammology Protocol
Dr Vasquez introduces the "Functional Inflammology Protocol" at the 2013 International Conference on Human Nutrition and Functional Medicine (PDF brochure)
Dr Vasquez's "functional inflammology protocol", famously recalled by the FINDSEX ® acronym, is reviewed in this presentation for its application to the three general types of inflammatory diseases/responses: 1) metabolic inflammation, including glial activation and emphasizing the component of mitochondrial dysfunction, 2) allergic inflammation, including asthma and eczema, and 3) autoimmune inflammation, including rheumatoid arthritis, psoriasis, and the many other conditions that Dr Vasquez has detailed in his books starting in 2004 (Integrative Orthopedics) and 2006 (Integrative Rheumatology, now published as Inflammation Mastery, 4th Edition).
Not simply a "book": 1,182 pages in color + more than 20 hours of video access
Discount via ICHNFM.ORG: US$170 plus shipping and handling (retail: US$250 plus shipping and handling)
Updates: Includes and bypasses everything from the previous editions published as Integrative Rheumatology (2), Naturopathic Rheumatology, Functional Inflammology and Functional Medicine Rheumatology; complete overhaul/expansion/update of the migraine and fibromyalgia protocols.
Inflammation Mastery 4th Edition provides everything from laboratory interpretation to the details of fatty acid biochemistry and mitochondrial dysfunction and hormonal imbalances/correction in one convenient location with a complete index. Also available as a two-volume set titled Textbook of Clinical Nutrition and Functional Medicine.
Peer-reviewed: Yes, as you can see in the PDF sample on page 6; see also: