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BrianMDelaney

Usefulness of personal genomics

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Peg asked why I decided to go on more severe CR. One reason is a risk for hypertension, which I have in spades. I've always wondered why, on what I thought was fairly serious (though not as severe as possible) CR, my BP was generally 125/70. 125/70 is fine, but it's not a typical CR value. Now I know why my BP isn't very stellar. Having now dropped my intake by around 100-150 calories/day, my BP is around 110/65 on average.

 

Another reason is that I discovered I have two SNPs in MTHFR that influence homocysteine levels negatively. Taking l-methyl-folate can help, but so would more CR.

 

And there are lots of other little disease risks. The great thing is that every single one of them can, according to research in laboratory animals, or in humans (according to biomarkers, and some epidemiological and even clinical data), be modified with CR.

 

Best,

Brian

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And there are lots of other little disease risks. The great thing is that every single one of them can, according to research in laboratory animals, or in humans (according to biomarkers, and some epidemiological and even clinical data), be modified with CR.

This pretty much sums up the benefits of CR. Other than perhaps a few diseases, and a few fairly benign side effects some may personally want to avoid, CR seems to dose-response improve or reduce risk for just about everything. It's not easy though!

 

I'm surprised your BP responded so much to a 100-150 kcal drop, but we all have our individual differences. I'd imagine this is more pronounced at the lower end of the calorie spectrum. How much of an increase would you expect if you were to increase you kcal by 100-200 from you previous level, or perhaps I should ask what your healthy ad lib BP is?

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I'm surprised your BP responded so much to a 100-150 kcal drop, but we all have our individual differences. I'd imagine this is more pronounced at the lower end of the calorie spectrum. How much of an increase would you expect if you were to increase you kcal by 100-200 from you previous level, or perhaps I should ask what your healthy ad lib BP is?

 

Hi James,

 

My siblings, one slightly younger (48), one slightly older (almost 51), have BPs of around 160/100 without meds. Neither is overweight by conventional standards, so, looking at my SNPs, I'd guess that, if I weren't on CR, my BP would be the same as their non-medicated BP. In my late twenties, before I went on CR, I was exercising intensely, had a BMI of around 22, and had a BP typically of around 130/75. (I remember my siblings both needed to go on meds in their late 30s; they were OK in their 20s.) Uncontrolled hypertension is really bad news, esp. for the brain, so for that reason alone, I'm glad I went on CR. And you've got an additional motivation, as, I'm guessing, do I, thought my ApoE results are still "sort of locked" (long story).

 

Brian

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I'm not surprised by Brian's experience with BP. I've found that CR isn't really so continuous or dose dependent as we think. If you're not below your set point, the obvious effects of CR don't really seem to appear. Maybe this is the reason that Dr Walford et al. came up with the idea of the set point. To refine the concept a little bit, maybe the set point is the point at which the constellation of CR biomarkers starts to align or maybe becomes aligned.

 

The Constellation of CR Biomarkers

  • Lower Body Temperature
  • Lower BP
  • Lower resting heart rate
  • Lower C-Reactive Protein
  • Higher HDL
  • Lower LDL
  • Lower Total Cholesterol
  • Lower Triglycerides
  • Lower Testosterone
  • Lower IGF-1

There may be more, like thyroid hormone measures and blood counts etc, but I think if you have maybe 8 or 9 out of those biomarkers working for you at the same time as you're cutting calories, then you're in "CR mode" and will generate the robust health that CRON practitioners are know to have.

 

 

I started thinking about this last fall when I fell off a ladder and broke a couple of ribs. I stopped my CR practice for a while in favor of a higher IGF-1 diet to encourage faster healing. When I went to get back on the CR bandwagon, I found that I had to cut 100 - 150 calories off my previous intake in order to get any weight reduction at all (+ 10 lbs during my convalescence and my LDL had shot up from 80 -> 106 also) So I was wondering why I couldn't get any results with anything intermediate? 1750 calories -> no changes, 1600 calories -> changes occur , 1700 calories -> no changes. It's like there is a sticky point in the calorie continuum where you don't get CR changes.

Edited by keithsct

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Guest Allen Taylor

Brian, you say:

 

 

Another reason is that I discovered I have two SNPs in MTHFR that influence homocysteine levels negatively. Taking l-methyl-folate can help, but so would more CR.

 

 

This is interesting and may be important. How can I extract important information from my 23andMe data beyond what they report in their health info, as you have done?

 

Allen

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I ran my 23 and Me data through

Promethease (a free download for windows)

and came up with this for MTHFR http://www.snpedia.com/index.php/Gs192

 

 

You have a combination of 2 SNP variations in MTHFR which influence homocysteine levels. A study of 37,026 individuals found that 19.8% of the participants had at a single copy of a mutation in both SNPs. An additional 0.08% had a double copy of a mutation in one of the SNPs, and a single mutation in the other. [PMID 15834246] People with gs193 who have double mutations in both genes are believed to be critically impacted.

Which is probably similar to what Brian is talking about.

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Keith- Yes, gs192 (internal SNPedia nomenclature) is exactly what I have. Not rare, but worth taking seriously, esp. if one's homocysteine levels aren't stellar.

 

Promethease is a great tool! 23andMe only reports on findings that are well established (and a few they call "preliminary"). There's much more useful info available with your nearly 1 million SNPs. As part of my research for the CR Society's evolving DNA HACR (DNA, Healthy Aging, and CR) project, I've been learning about some of these other tools and projects. I'll report on them when I know more.

 

Brian

 

P.S. I'd recommend paying the $2 for the enhanced Promethease report:

 

http://www.promethease.com/index.php/Promethease

 

Also, the free version takes 4-7 hours to run. The paid version completes in 5-10 mins., as I recall.

Edited by BrianMDelaney

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>

> I'll post about my own decisions late tonight or tomorrow.

>

> Best,

> Brian

 

I'm still trying to use our forums. So, continued here:

 

Ok, I'm a bit confused about continuing here, as the 2 "original" CR email lists (after Yahoo) seems to have been "deactivated" from posting directly "there" anymore. Yet, people are using their email accounts to continue posting "the conversations" there rather than over here???

 

Will these split-up posting locations, email lists vs forum posting, transition and close down to final posting location(s) soon, so we can gather to read in one place to find information faster? Or, are there other plans in the making?

 

Thanks.

Edited by Sara2

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As part of my research for the CR Society's evolving DNA HACR (DNA, Healthy Aging, and CR) project, I've been learning about some of these other tools and projects. I'll report on them when I know more.

 

Are there any threads started now that someone can recommend to get up to date on gene tests relating to CR?

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Has anyone analyzed which test(s) are best for CR or disease inheritance markers or longevity factors/markers? Who are our resident experts?

 

Some Genetic Tests Available

 

Testing

 

Consumer genotyping

 

23andMe uses a customized Illumina chip which covers 18022 of the 36592 snps in SNPedia. $99 one time payment, lifetime membership

FamilyTreeDNA uses an Illumina OmniExpress for autosomal ancestry testing at a $289 price point, including raw data download. It covers 3931 of the snps in SNPedia.

Pathway Genomics offers various kits for Ancestry and Health, but seems not to release raw data and so isn't of much use with Promethease.

Complete Genomics offers full human genome sequencing for $5k as a service for researchers.

Knome offers direct full genome sequencing for $95,000

The Personal Genome Project aims to recruit 100,000 volunteers and publish their genomes and medical information

Coriell Personalized Medicine Collaborative is free, but returns information on only 30 snps which meet IRB approval

Illumina http://everygenome.com web site

 

Genetics & Public Policy Center Aug 2011 list of DTC companies

 

Alpha by Disease

by disease category

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Sara, Sorry for the confusion about where to post what! We're in a transition phase, and many of us are trying to use these new web forums, just to see how it feels. I'm going to continue mostly here.

 

As for which testing service to use, 23andMe is by far the cheapest of the non-full sequence services. I would recommend them. And then join the Personal Genome Project at Harvard, and hope they get funding to do a full sequencing of your genome! (Your odds of being sequenced go way up if you have other family members who also join.)

 

Best,

Brian

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Hi Brian,

 

Thank you very much for the detailed update.

 

Do you know off-hand if these tests or studies can use a hair sample?

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Do you know off-hand if these tests or studies can use a hair sample?

 

Pardon the delay! Was side-tracked with a bad case of food-poisoning....

 

23andMe uses saliva. Not sure about the other companies. Drooling into a test tube was fairly painless, I must say.

 

Best,

Brian

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I did the Pathway Fit test from Pathway genomics and I am finding their report to be very useful.  It mostly confirms many of the results of my own self experimentation with diet contents and activity.  The test is designed to give you very actionable recommendations about activity types and levels and dietary content.  To give you some idea, the test tells me that I am inefficient at metabolizing many B vitamins, folate, C, and EPA/DHA.  Replacing sat fat with poly is more beneficial than is typical.  I might lose muscle mass from resistance training, but moderate endurance exercise is especially beneficial.  I have a lot of negative markers related to cholesterol, but great insulin and glucose markers. I am lactose tolerant and a fast processor of caffeine and unlikely to have any negative side effects for caffeine.

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All,

 

We've had quite a bit of discussion recently (although not on this thread) about the usefulness of genetic testing. Here is an interesting discussion with a researcher involved in genetic screening, who gets a bit flummoxed when the interviewer points out some of the ethical / psychological concerns for his human subjects. One the one hand he's collecting a ton of data on his subjects (using full genome sequencing) which could be very valuable to his subjects for learning about their genetic susceptibility to various diseases. What if he fails to disclose something important to them, learned through the genetic tests but irrelevant to the study he's doing? And what if the data he collects is used to deny people life insurance due to their genetic susceptibility to certain illnesses? And what if he discovers and discloses something to a subject (like they have the BRCA gene for breast & ovarian cancer) but they didn't want to know? All very difficult questions...

 

Fascinating interview, with a transcript for the impatient.

 

--Dean

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Cool, Dean -- thanks.

 

Personally, I see no downside to researchers saying to patients/subjects: "We may see other genes that have clinical significance, pos. or negative. Wanna know about those?"

 

- Brian

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Brian,

 

Personally, I see no downside to researchers saying to patients/subjects: "We may see other genes that have clinical significance, pos. or negative. Wanna know about those?"

 

That seems right to me. In the case of a responsible adult, it seems that informed consent to either disclose or withhold genetic information based on the subject's preference is the right way to go. But what about when it's your young child's genetics, and their future health vs. their future ability to get life insurance, that is at stake? That seems like a much harder question for a parent to answer.

 

But now that I think about it, it doesn't seem quite so cut-n-dried with the adult either, and this seems to apply to all medical studies / interventions, not just personal genetics.

 

Suppose you are a researcher who collects data and could easily determine if someone has a life threatening condition. If you look at that information and see that they have the condition but don't tell them, or if you choose to bury your head in the sand, as this researcher interviewed appears to do by not even looking to see, for example, if a woman has the BRCA gene despite having the information at his fingertips, are you doing something wrong? Is it ethical not to share that information with the patient? Or are you ethically obliged to share that information with them? Perhaps more practically, in our litigious society, could the subject come back later and sue you (and win!) for not having disclosed to them information that could have prevented them or their family much pain and suffering?

 

It seems quite analogous to a radiologist who reads the CT scan of someone's abdomen because of concern over possible liver polyps, and misses seeing a large and obvious kidney tumor clearly visible on the same scan. If they patient sues the doctor, will the defense "It wasn't my fault I missed that obvious kidney tumor, I was only intending to look at the liver" fly with a jury?

 

--Dean

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Well - I didn't have to look very hard to find the answer to my question about the culpability (at least in the eyes of the jury) of a radiologist who missed an easy-to-detect tumor. Here is a story about just such a case:

 

A jury has awarded $16.7 million to the daughter of a Boston woman who died of lung cancer after a radiologist missed evidence of the cancer in a chest X-ray.

 

[The radiologist's lawyer] said [the radiologist] was able to see areas of opacity in the chest X-ray when he reviewed it after [the plaintiff/patient's] cancer diagnosis, but those areas could have been attributed to a number of things, such as tissue structures or other organs. He said that a chest X-ray is not the best tool for spotting lung cancer and that [the radiologist] was not provided with [the patient's] full medical history, which included a 30-year history of smoking and a mother who died of lung cancer.

 

Apparently the jury didn't buy it, or they felt bad enough for the victim's family that they awarded them $16.7M anyway, knowing it would be paid by the malpractice insurance company of the radiologist or his hospital, and not the radiologist himself.

 

It seems like the same thing could happen with personal genetic testing. Researchers could be damned if they do tell subjects of anything bad they find - and the patients later say 'I didn't want to know' or 'I wasn't fully informed of the financial/physical/psychological harm such disclosure would later cause' and they are damned if they don't tell subjects of anything bad they find - and the patient later sues for negligence like the above lung cancer patient's family.

 

--Dean

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All,

 

I'm not sure if this is a big advance, or just an incremental improvement, but I know that for many years they've been talking about eventually getting full genome sequencing for less the $1000. It appears that that day may have finally arrived, according to this new announcement by Veritas Genetics (popular press story). It looks like the key difference between what VG is offering and the previous $1000 genome sequencing announcement by the other big player (Illumina) is that VG is offering not just the testing, but also complete results and genetic counseling / interpretation for that $1000:

 

According to Veritas, the test includes a digital report and app where you can view your results, video-based genetic counseling, and lifestyle-relevant information (related to fitness or nutrition, for example). It also includes access to expert opinions from physicians at Massachusetts General Hospital, Dana Farber Cancer Institute, Boston Children's Hospital, Mayo Clinic, and others.
 
Veritas is not a direct-to-consumer test. It requires you to order it through your doctor. However, you can place a pre-order now through the Veritas website, pending your doctor's approval.

 

--Dean

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