{"id":1281,"date":"2017-04-20T11:54:48","date_gmt":"2017-04-20T11:54:48","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1281"},"modified":"2017-08-21T10:17:02","modified_gmt":"2017-08-21T10:17:02","slug":"primary-care-corner-with-geoffrey-modest-md-23andme-genetic-analysis-approved-for-direct-advertising","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2017\/04\/20\/primary-care-corner-with-geoffrey-modest-md-23andme-genetic-analysis-approved-for-direct-advertising\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: 23andMe genetic analysis approved for direct advertising"},"content":{"rendered":"

\u00a0by Dr Geoffrey Modest<\/strong><\/p>\n

The FDA just approved direct-to-consumer marketing for genetic risk information (23andMe Personal Genome Service Genetic Health Risk) for 10 conditions, though noting that “the tests cannot determine a person’s overall risk of developing a disease or condition … there are many factors that contribute to the development of a health condition, including environmental and lifestyle factors.” This approved test involves saliva samples, assessing more than 500,000 genetic variants associated with increased risk of: Parkinson’s disease, late-onset Alzhemer’s, Celiac disease, Alpha-1 antitrypsin deficiency, Early-onset primary dystonia, Factor XI deficiency, Gaucher disease type 1, Glucose-6-phosphate dehydrogenase deficiency, Hereditary hemochromatosis, Hereditary thrombophilia. see\u00a0https:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/ucm551185.htm<\/a>\u200b<\/p>\n

The FDA reviewed the data for 23andMe through a premarket review pathway\u00a0for low-to-moderate risk devices, with expectations about assuring\u00a0test accuracy, reliability and clinical relevance, and also to make sure\u00a0the results be clearly understandable by consumers.\u00a0But\u00a0the FDA now intends to exempt further tests added on by 23andMe\u00a0from further\u00a0premarket review, and may well exempt other genetic testing companies\u00a0after submitting their first premarket notification. \u00a0These exemptions “would allow other, similar tests to enter the market as quickly as possible and in the least burdensome way”. [and, I might add, this is before confirmation of\u00a0Trump’s pro-industry FDA nominee Scott Gottlieb, who has “received millions of dollars from various investment and pharmaceutical firms” per Bloomberg Technology…..]<\/p>\n

Statnews had a really impressive review of the 23andMe test, at the cost of $199, revealing many of its limitations (see\u00a0https:\/\/www.statnews.com\/2017\/04\/07\/genetic-analysis-need-to-know\/<\/a>\u200b ). For example, they note that\u00a0those having the specific variant for Parkinson’s disease tested\u00a0increases their risk 3-fold, from a baseline of 0.3% to 1%…. Or, that those with Apo \u21074\u00a0alleles\u00a0may not get Alzheimer’s, and those without it may (the frequency of the\u00a0Apo\u00a0\u21074\u00a0allele varies by ethnicity, 15% in Caucasian, 25% African-Americans; the presence of one allele increases the risk of Alzheimer’s by 2-3 fold, and two alleles by 8-12 fold). \u00a0So, the presence of a genetic variant, either for the Parkinson’s gene or if only 1 allele of\u00a0Apo\u00a0\u21074, still makes the development of the disease unlikely (and actually rare, in\u00a0the Parkinson’s case). And still about\u00a010% or so of those who are homozygous for\u00a0Apo\u00a0\u21074 do not get dementia.<\/p>\n

Commentary:<\/p>\n

–the big issues here, to me, are:<\/p>\n

–these tests may well have pretty low sensitivity and\u00a0specificity, as well as low positive predictive value<\/p>\n

–patients may have trouble understanding the wording: 3x higher incidence of Parkinson\u2019s sounds like a lot, but the actual 1% incidence not so much. Can be very confusing<\/p>\n

–and, there are real concerns about the psychological effects of finding out one has a somewhat higher likelihood of a bad disease for which there is no current treatment. Will there be more depression, anxiety, decreased social cohesion\/more isolation, hopelessness\/even suicide?<\/p>\n

–focusing on the genes undercuts the very important role of\u00a0environmental\/lifestyle factors: it really\u00a0reinforces the conceptual\u00a0deterministic framework that one\u2019s future is set by one\u2019s genes,\u00a0undercutting\u00a0the oftentimes dominant message that our environment and lifestyle are really important<\/p>\n

–and it reinforces the conception that technology is the answer to our ills\u2026<\/p>\n

 <\/p>\n

————————————————————-<\/p>\n

Some recent article on dementia are tangentially related to the above.<\/p>\n

–The WHO reported that\u00a0dementia deaths have increased, unseating AIDS as one of the top killers in the world (see\u00a0http:\/\/edition.pagesuite.com\/popovers\/article_popover.aspx?guid=30673b53-29ff-49a5-a387-796e55c1aa5e<\/a> ),\u00a0and taking over the number 7 slot of the top 10 causes of death. And, as per this article in Bloomberg News, about 100 experimental treatments for dementia have failed to make matters better. Part of the issue causing the “elevation” of dementia is the aging population and probably that\u00a0it is more often diagnosed now. But, so far, drugs do not seem to be the answer<\/p>\n

–in this light, and complementing the above point that genes often do not play a decisive role, there was a recent study finding that lower adherence to\u00a0a Mediterranean diet was associated with more significant loss of brain volume (see Luciano M.\u00a0Neurology 2017;88:1)..<\/p>\n

–Background: increased adherence to Mediterranean diet (lots of fruits, veges, legumes, cereals, olive oil as primary fat, moderate consumption of fish, low to moderate intake of dairy and wine, and low intake of red meat and poultry) is associated with less\u00a0inflammation, better cognitive function, and lower risk of Parkinson’s and Alzheimer’s, as well as cardiovascular and cancer mortality. And cross-sectional studies have found higher consumption of components of the Mediterranean diet are associated with larger MRI-based brain volumes and cortical thickness. Higher fish and lower meat intake seemed to be the most important players.<\/p>\n

–The current study was a prospective one of 562\u00a0Scottish men and women, assessing diet and brain structural changes from age 73 to 76<\/p>\n

–50% female, 30% Apo\u00a0\u21074 positive, 4% diabetic\/38% hypertensive\/22% cardiovascular disease\/BMI\u00a028<\/p>\n

–baseline cognitive ability: Mini-Mental Status Exam 29 (30=max, so no significant baseline dementia), and they assessed reading ability\u00a0and general cognitive ability which relates to IQ (no comment on the scales they used or their validity).\u00a0Diet was assessed only at baseline, age 70.<\/p>\n

–change in brain structure from age 73 to 76:<\/p>\n

–total brain volume: decreased\u00a019 ml (from 990), gray matter volume decreased 9 ml (from 465), mean cortical thickness\u00a0decreased 0.05 mm (from 3.11 mm)<\/p>\n

–results:<\/p>\n

–the group with highest adherence to Mediterranean diet had more carriers of Apo\u00a0\u21074\u00a0alleles (reason for this unclear in this healthy population who did not have\u00a0underlying dementia), yet had greater total brain\u00a0volume and gray matter volume at age 76<\/strong><\/p>\n

–in the fully adjusted model (controlling for those factors found in prior studies related to Mediterranean diet and brain MRI measures: age, sex, education, BMI, diabetes, general cognitive ability, MMSE), there was significant association\u00a0between Mediterranean diet components and total brain volume change between age 73 to 76\u00a0(p=0.04), and presence of <\/strong>Apo\u00a0<\/strong>\u2107<\/strong>4<\/strong> genotype did not change this<\/strong>.\u00a0Fish and meat consumption were not found to be the drivers of this association. [perhaps it is a different combination, or even the all of the components together:\u00a0parsing out specific components may be a tad reductionist and\u00a0undercut potential interactions between the individual components. Better to eat well overall]<\/p>\n

–commentary:<\/p>\n

–so,\u00a0there was a significant\u00a0association between the diet and brain volume changes\u00a0over this 3-year period<\/p>\n

–and, the effect size of the Mediterranean diet on brain volume was substantial: half the size of that due to normal aging<\/p>\n

\u200b–of course, this was not a randomized controlled trial, so there could well be confounders (do those choosing to adhere to a more Mediterranean-type diet do other, unmeasured\u00a0healthful things that may\u00a0really be the ones that\u00a0decrease cognitive decline, such as exercise??)<\/p>\n

but, all in all, this study supports the concept of environmental\/lifestyle factors being really important in the development of Alzheimer’s\/cognitive decline, that this appeared to be\u00a0 independent of the known genetic risk factor of\u00a0Apo\u00a0\u21074\u200b\u200b, and adds to the argument against a genetic-determinant view of the development of this important condition (as is conceptually promoted by 23andMe etc)<\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

23andMe genetic analysis approved for direct advertising […]<\/p>\n

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