Monthly Archives: June 2011

Interpretome

The Interpretome project at Stanford University is a very useful set of tools from an awesome team of graduate students studying bioinformatics and biology.

Here are some recent posts from genetics bloggers about the Interpretome project:

• Blaine Bettinger – Interpretome: New Analysis Software for Autosomal Testing Results

• Daniel MacArthur - Interpretome: new online tools for analysing personal genome data

• Razib Khan – Beyond, the Interpretome!

Here’s a brief guide on getting started with the site:

1. Make sure you’re using the Chrome or Firefox browser (I used Chrome on Snow Leopard).

2. In the upper right hand corner of the screen, click the Choose File button to load your unzipped raw data that you downloaded from 23andMe or Lumigenix.

3. The information will be parsed. The process was very fast for me – only about ten seconds on a cable internet connection.

4. Select your population type from the drop-down menu in the upper right hand corner of the screen.

The tabs on the site give you these options:

• Lookup – you can look up individual SNPs in your genotype file

• Explore – you can see the interpretation of several traits (eQTLs, positive selection, Neaderthal alleles, exceptional longevity, height)

• Clinical – you can profile your risk for a disease and get pharmacogenomic information (Type 2 diabetes, GWAS variants for certain diseases, warfarin dosing, and pharmacogenomic variants)

• Ancestry – you can check similarity compared to members of the Interpretome team, ancestry by principal component analysis, and chromosome painting

Here are some PDFs that show the site in action:

Chromosome Painting

Diabetes Risk

Exceptional Longevity

GWAS Variants

Pharmacogenomics

Updated Genetic Information on SNPedia

SNPedia is a very helpful resource for genetic information. It’s a wiki that includes information on human DNA. The information from SNPedia is used by Promethease to generate useful reports on variations in DNA. I talked more about Promethease in this post:

New Promethease Report

SNPedia also has downloadable data from people who publicly shared their genetic information. Raw data from 23andMe along with corresponding Promethease reports can be found in this section of the wiki:

Genomes – SNPedia

The site currently lists 102 public genomes, including mine:

User:Samsnyder

It’s awesome to be on the forefront of personal genetics, with my data hosted alongside people like:

• Craig Venter, human genome pioneer

• James Watson, co-discoverer of the structure of DNA

• George Church, professor at Harvard Medical School

• Linda Avey, co-founder of 23andMe

23andMe and Alzheimer’s Risk

23andMe is using a new chip to analyze genetic information. One of the major features is its ability to provide predictive guidance on a person’s chances of getting Alzheimer’s disease. This is based on variations in the APOE gene, which have been widely studied.

Here is a PDF of a section of the 23andMe website that shows how the results are presented:

Disease Risk – Alzheimer’s Disease

The genetic information used to generate that page comes from me.

It can be unnerving for people to see information like that – especially people who are age 50 or above. For someone in his 20′s like me, the information on Alzheimer’s isn’t necessarily as urgent. I’m not a genetic counselor, but I think someone in an older age group should think particularly hard about whether to view the results (23andMe makes it so that you have to go through several pages of confirmations, rather than just being able to see your Alzheimer’s risk right away).

I can live with a 14% chance, which is twice the average risk. I was worried the odds would be something like 40% or 80%. I have a document in Google Docs where I put medical research topics on a to-do list. The list covers a number of topics that I want to research on PubMed. My list has keywords that relate to topics like increasing testosterone naturally and evidence-based methods for reducing stress. Alzheimer’s disease is now on that list.

I haven’t actually done a search of PubMed or even science news sites to go through the thousands of research abstracts that relate to promising ways to prevent or treat Alzheimer’s disease. In the meantime, here are a few tips for brain health and Alzheimer’s prevention that I’ve read recently:

• Spices like curcumin may help prevent Alzheimer’s. That may be why people in India have only a quarter of the risk of Alzheimer’s of same-age Americans.

• Keeping blood sugar stable might also help. New research is showing that Alzheimer’s disease may involve metabolic abnormalities just like diabetes:

- Nutrition and Alzheimer’s disease: The detrimental role of a high carbohydrate diet (PDF)(credit: Zooko)

• Contrary to popular dietary advice, the brain thrives on cholesterol and saturated fat. That’s why statin drugs can contribute to memory loss.

• A ketogenic diet may be protective against Alzheimer’s disease. Studies show that ketosis enhances memory:

- Dietary ketosis enhances memory in mild cognitive impairment (PMID: 21130529)

• Alzheimer’s may be caused due to bacterial infections. If that’s the case, here are some options for prevention: Eleven Steps for Overcoming Alzheimer’s and Other Chronic Infectious Diseases

New Promethease Report

In my last post, I discussed getting my new results from 23andMe using the updated v3 chip they use to analyze genetic information. You can see the post here:

New 23andMe Data

I then ran my data through Promethease to generate a new report, which can be downloaded here:

• http://files.snpedia.com/reports/genome_Sam_Snyder_Full_20110604122322.html

Promethease is a very useful application for analyzing the raw data from 23andMe and finding out more extensive information about the SNPs (single nucleotide polymorphisms) in your DNA. It generates reports based on data from SNPedia, a wiki that investigates human genetics and has entries about variations in DNA and their effects on health.

The application is very easy to use:

1. Download your raw DNA from 23andMe.

2. Open Promethease and import the raw data file.

3. Click Next.

The time to process the information varies. If you pay a small fee via Amazon payments, Promethease will run faster. Otherwise, it will take about five hours to fully generate the report.

DNA isn’t destiny. One of the best ways to illustrate that is the sometimes conflicting results that appear in reports from 23andMe and Promethease. An analysis of a person’s DNA will mention one study that shows an increased risk associated with a certain SNP and another study that shows a decreased risk associated with another SNP. A person’s environment can also contribute to the development and expression of certain traits.

New 23andMe Data

I recently downloaded my new raw data from 23andMe and am making it publicly available. This genetic data was generated using the latest v3 chip, which allows them to provide predictions for Alzheimer’s disease risk based on markers in the APOE gene.

Two bloggers in the genetics world have good overviews of the new update:

• Razib Khan: 23andMe v3 Chip & Me

• Dr. Daniel MacArthur: 23andMe Releases Results for Major Alzheimer’s Risk Marker

As with the v2 version of my raw data from 23andMe, I uploaded the raw data to a public Dropbox folder for anyone to download and explore using bioinformatics tools.

Here’s the link:

http://dl.dropbox.com/u/8013395/genome_Sam_Snyder_Full_20110604122322.zip

The Nutrition Portfolio

Conflicting information often appears on science and medical news sites. One day some nutrient seems like a panacea, but a few months later it gets depicted as ineffective or even dangerous. Here’s a strategy for improving the situation.

1. Going through nutrition journals – or even scientific news sites like PhysOrg and Eurekalert – to find superfoods that have various benefits for health and longevity.

2. Incorporating those foods into meals in a rotating fashion. This leads to greater food diversity and hedges bets to reduce the risk of eating a certain food at a majority of meals. By not eating the same food at every meal, you reduce the risk of developing allergic reactions to it. Another benefit is that a diverse portfolio of meal plans can reduce the risk in the case later research shows a certain superfood to be dangerous or have unintended consequences.

3. Using an artificial intelligence system like Watson or Eureqa to model all of the effects of different nutrients at a cellular level, as well as their effects on the human genome and proteome. This will find the optimal diet for human beings in general in addition to better ways of tailoring nutrition to specific individuals.

Scott Locklin on Tim Ferriss

I’ve been reading Tim Ferriss’ book The Four Hour Body for the third time (see my notes on the book). I also recently discovered Dr. Scott Locklin’s Amazon reviews, which are informative and enjoyable to read. Locklin is a physicist who went the quantitative finance route and who sometimes blogs about the use and misuse of science. Here’s his review of The Four Hour Body:

Where He’s Right, and a Lot of Places Where He’s Wrong

After reading that review, it was like having some of my own reservations about the book distilled into a cogent argument. The first time through the book, I was incredibly impressed. The third time through the book, my critical thinking faculties started to come online. The review would definitely benefit being turned into a blog post with some actual research citations, but it’s still very informative and entertaining.

I really enjoy Dr. Locklin’s thoughts on science, which he writes on his blog:

Locklin on Science

A lot of times when reading his blog posts, like the ones about nanotechnology and Nassim Taleb, I start to think: “you know, he’s right about this!” I’m not sure I currently agree with all of his thoughts that he posts on sites like Alternative Right and Taki’s Mag, but that may be due to my general dislike of political topics after getting screwed over by believing in what the political Left and Right were saying at various times. Who knows, I may end up agreeing with him on aspects of society and politics and how to run the world someday.

I basically think that physicists should lead the world, so it’s a good idea to tune into what they’re saying – both about physics and about other topics as well. The sheer brainpower of physicists often gives them a greater precision and accuracy than pundits and cultural commentators.

Ketogenic Nutrition

In this post I’m going to talk about ketogenic nutrition and why it’s useful for some people and not necessary for others. First, here are some brief guides to ketogenic diets:

• Dr. Emily Deans: Your Brain on Ketones

• Dr. Joaquin Perez-Guisado: Arguments in Favor of Ketogenic Diets

• Joseph Arcita: A Guide to Ketosis

• Dr. Michael Eades: Metabolism and Ketosis

The body goes into a state of ketosis when carbohydrate intake is restricted below a certain level. This is not to be confused with ketoacidosis. It’s an important point to make, and it seems like every low carb book is contractually obligated to make that distinction. Ketogenic diets are used in these major scenarios:

• Epilepsy – Ketogenic diets have been used for nearly a century in treating pediatric epilepsy. Going into ketosis can reduce the frequency and severity of seizures for some patients. The fifth edition of the book Ketogenic Diets by Dr. Eric Kossoff is scheduled to be released soon and includes more information on the subject.

• Cancer – Research conducted by Dr. Thomas Seyfried shows that malignant brain tumors are unable to rely on ketone bodies for energy. This makes brain tumor cells more vulnerable. I wrote about the topic further in my posts Ketogenic Diet Treatment of Brain Cancer and Can Ketogenic Diets Cure Cancer?

• Weight loss – The books by Dr. Robert Atkins promote ketosis as a way of resetting the body’s metabolism and jumpstarting the weight loss process. Some people have had success with this method, while others have had less success.

• Diabetes – A group of researchers showed that a low carbohydrate ketogenic diet allowed patients with type 2 diabetes to lower the amount of medication they required. Ketogenic diets can also reverse diabetic nephropathy.

• Migraine - Dr. Larry McCleary is a neurosurgeon who also discusses the ketogenic diet as a treatment for migraine in his book The Brain Trust Program.

• Alzheimer’s Disease – So far, there haven’t been many tests of using ketogenic diets for treating Alzheimer’s disease. One of the only experiments I know of comes from Dr. Mary Newport, who tested coconut oil on her husband. This is just a test involving one person, but if Alzheimer’s is actually a form of Type 3 diabetes that involves blood sugar abnormalities, then maybe ketosis could help improve brain function in patients with Alzheimer’s disease. Don Matesz studies the evidence further in his post Meat is Medicine.

Tim Ferriss recently introduced ketogenic nutrition to a wider audience. He references data from bariatric physicians Drs. Michael and Mary Dan Eades, who are major figures in the world of low carb nutrition. Ferriss mentions in his book The Four Hour Body that the cyclical ketogenic diet made him look incredibly lean and muscular and was the only diet that increased abdominal vascularity for him (where you can see veins popping out on a person’s body, as many bodybuilders demonstrate).

Science writer Gary Taubes recently posted his blood test results. He has very good numbers while eating lots of fat and very little carbohydrate. After reading books like The Great Cholesterol Con, though, I’m more skeptical of conventional lab measurements. Measuring indicators that relate to blood clotting seems like a more promising way of preventing heart disease.

After reading all of this information about ketogenic nutrition, I was really gung-ho to give it a try. Then I found out that while ketogenic diets are useful for people facing specific medical problems, they probably aren’t necessary for most people. Lipid researcher Mary Enig says in her book Eat Fat Lose Fat that ketosis can lead to nausea, fatigue, dizziness, and abnormal heart rhythms.

Other good information comes from the following two bloggers, who skeptically examine low carb diets as well as the standard American diet:

Anthony Colpo – a trainer and independent researcher who really knows his way around the scientific literature

Evelyn Kocur - a blogger with a scientific background who also knows how to analyze nutrition studies in detail

These writers seem to lean more towards paleolithic nutrition. The paleo diet is gaining plenty of backing from physicians and researchers. You can search for the word “paleo” in my blog archives to find some posts where I discuss the scientific rationale behind eating like early hunter-gatherers. In a nutshell, paleo researchers argue that the human genome hasn’t really changed all that much in the past 100,000 years and human beings still function best on foods that match the ones used by early humans.

I think there will still be some variation between people from different ethnic backgrounds, which is where the field of nutrigenomics comes in. One of the results included in my DNA test from 23andMe focused on nutrition. It said that people with SNPs (single nucleotide polymorphisms) similar to me will lose weight on a high fat diet but not a high carb diet. The impact of different foods on gene expression is one of the most exciting areas of science.

The following search string for PubMed is a good way of keeping up with research on ketogenic nutrition and ketosis:

ketogenic[title/abstract] OR ketosis[title/abstract] OR ketone[title/abstract] OR ketones[title/abstract]

Those search results look pretty overwhelming at first glance. The good news is that you can then adjust the search further, such as by using PubMed’s limits feature to limit the results to studies in humans for example. If you use Google to find results for “searching PubMed” or “using PubMed” you can find lots of helpful guides to searching PubMed and narrowing down searches.

Updated 12/11/2011

The Biology of Mark Zuckerberg

Mark Zuckerberg achieved financial success far beyond the majority of people twice his age. His $100 million donation to the Newark education system demonstrates this. Zuckerberg also received the honor of being named Time Magazine’s person of the year. Zuckerberg’s accomplishments are worthy of praise, but he’s not a self-made man. He’s the son of a psychiatrist and a dentist. Considering that a fairly small percentage of Americans go on to get a professional degree, he’s the product of two people with high intelligence. There’s evidence from studying identical twins that intelligence and conscientiousness have large genetic components.

An interview with Dr. Arthur De Vany describes the psychological damage incurred from comparing yourself to celebrities or business superstars. In human history, people lived in small tribes and had limited social reference points. Now people have the opportunity to compare themselves to thousands of people who each appear perfect in some way.

Genes don’t totally determine the outcome of a person’s life, but they have a major influence. For years physics professor Steve Hsu has been documenting the impact of genetics and IQ on a person’s life. His most relevant blog posts to this discussion are in these categories:

• Information Processing: genetics

• Information Processing: iq

Some people get nervous when talking about genetics and intelligence, because they worry – and rightly so – that it could be used as justification for eugenics or selective human breeding. However, eugenics is an unethical blunt instrument, especially when there’s the possibility that medications and therapies for cognitive enhancement could be available in the next couple of decades. Would you really want to deny existence to the hypothetical person who could save the world if they received the right medication?

I think the right answer to this dilemma is focusing on improving human intelligence in easy ways that could bring about major benefits to a society. Are people really responsible for their actions if they have low impulsiveness due to nutrient deficiencies, abuse, and lead poisoning from when they were children? Improving childhood nutrition and environmental safety could greatly enhance the competitiveness and well-being of a community or nation. Even if an individual is predisposed to problems due to genetics, early intervention can set his or her life on a positive track. Neuroscientist James Fallon is a great example:

• A Neuroscientist Uncovers a Dark Secret

Zuckerberg admirably donated $100 million to the school district of Newark New Jersey. I’m going to explain where he should have donated his money, and why he probably had no real choice in the matter. Education is important to the future of the country, but there’s a growing belief that the current public education system is deeply flawed. Professor Peter Gray writes excellent criticism of schools and how to improve them in his Psychology Today blog Freedom to Learn. Schools are artificial environments that magnify status games among adolescents and often create or accelerate the development of mental illness. Some of his findings:

• Schools are like prisons.

• Schools are ineffective in dealing with bullying.

• Schooling may be behind the dramatic rise in anxiety and depression.

Also, graduate students in education have the second-lowest GRE scores among American graduate students. Schools are run by some of the dumbest “educated” people in the nation. Many students would be better off just staying at home and watching videos posted by physicists and mathematicians on YouTube. Schools would be better served by hiring fewer administrators and using the cost savings to raise teacher salaries to attract more qualified employees.

Zuckerberg would have been better off donating his money to virtual schools or starting a chain of for-profit education centers that utilize evidence-based research on how the brain learns. Harvard professor Clayton Christensen wrote an excellent book titled Disrupting Class about how schools are ripe for competition, disruption, and creative destruction. Even better, the Facebook CEO could have followed Bill Gates’ lead and saved millions of lives by investing in global health.

Many people claim Mark Zuckerberg donated money to education to distract from the negative publicity surrounding the movie The Social Network, as well as from some embarrassing emails and stories that leaked out about the early years of Facebook. That may have played a part in his decision, but I’m not convinced it’s the total story. The real motivation comes from the uneasy relationship between Facebook and schools. Many schools have started to block Facebook to cut down on wasted time and bullying. This donation is a form of protection money to improve Facebook’s image in the minds of the education cartel.

I’m mildly obsessed with Mark Zuckerberg since he’s almost the exact same age as me (he’s about a month younger than I am) yet he’s accomplished so much more in business and in life. He leads one of the most successful companies in the world, lives in one of the best cities in the United States, has a multi-million dollar home, and is a major philanthropist. Some people are even more obsessed with details about Zuckerberg’s life than I am, namely Pradeep Manukonda.

When I talk about famous people, it’s a way to explore aspects of trends and scientific findings by using their life as an example rather than an obsession with the person themselves or with gossip about them. One of the latest stories to amuse people in the business press is Mark Zuckerberg’s latest goal of eating only meat from animals that he personally kills:

Mark Zuckerberg’s New Challenge

Opinions vary regarding Zuckerberg’s commitment to local food and personal involvement in preparing what he eats. Some people are confused, others are supportive, and still others are horrified and angry. I definitely respect Zuckerberg’s idea of a yearly challenge. In January, I blogged about my own yearly challenge of reducing inflammation. The idea for the challenge came about after reading thousands of pages of medical information and discovering that chronic inflammation is connected to many forms of illness and mental stress.

There are two major points I want to discuss about Mark Zuckerberg’s goal:

• The impact of offbeat personal preferences on company PR

• The impact of vegetarian diets vs. omnivorous diets on cognition and brain health

A highly visible CEO can either add to or detract from a company’s performance. Companies like Apple and Facebook can have thousands of employees, yet many people still only think of Steve Jobs or Mark Zuckerberg when they think of those companies. In some cases, it can be important for a public relations team to hide a CEO’s personal preferences and idiosyncrasies. Executives who publicly talk about their political beliefs and innermost thoughts risk alienating the millions of customers who don’t agree with them. Executives who say seemingly creepy things, as former Google CEO Eric Schmidt did when talking about privacy, are often best elevated to the level of chairman. That opens up the opportunity to install a new CEO who only tells investors and customers what they want to hear.

The news about Mark Zuckerberg’s dietary preferences also got me thinking about how vegetarianism compares to a more varied diet when it comes to cognitive performance. The articles about his new diet said that he eats a mostly vegetarian diet, since he’s busy running a $100 billion company and can’t spend too much time getting involved in killing animals every day.

After reading about the diverse set of nutrients in meat and their contributions to heart and brain health, I’m somewhat skeptical of vegetarian diets. People still may be able to make a vegetarian diet work for them and be as healthy or even healthier than omnivores, but they’re missing out on the benefits from important nutrients in meat like carnosine and carnitine. My hunch is that a vegetarian who eats lots of green vegetables, omega 3 eggs, and coconut products will be much healthier than a vegetarian who eats mainly grains, sugar, and soy. This is based on new scientific evidence that shows the health importance of saturated fat (which makes up most of coconut oil and has been unfairly demonized in the past) and the antinutrient properties of grains and soy (which have been embraced due to faulty scientific evidence). Coconut oil is the best vegetarian/vegan form of fat that I can think of.

I haven’t studied the impact of vegetarian diets on mental health in great depth, but here are a couple of interesting case reports that give me pause:

Schizophrenia-like psychotic episode precipitated by cobalamin deficiency

Psychiatric manifestations of vitamin B12 deficiency

Dr. Emily Deans is a psychiatrist who frequently blogs about the importance of meat, fat, and cholesterol and their role in brain health. She links to scientific studies that disprove commonly held beliefs about cholesterol levels. Dr. Deans also describes the benefits of eating more fat and fewer grain products and the benefits that dietary changes can have in relation to mental health. Time will tell whether Mark Zuckerberg’s passion for preparing meat and his mostly vegetarian diet will have any impact on Facebook’s future and his ability to lead the company.

Update: FB has lost 60% of its value as measured in market capitalization since the IPO. This was probably due to Facebook being overvalued in the first place rather than the CEO’s diet. It would still be interesting to have a company where the executives and workers identify and implement an evidence-based diet and lifestyle that maximizes mental performance

Updated 9/2/2012

How to Use Bodybuilding Forums

When I search for health topics on the web I often come across information from bodybuilding forums. It’s understandable since bodybuilding.com is one of the most popular and extensive forums on the web. The information found on bodybuilding message boards varies in the level of accuracy. Sometimes there are helpful graduate students in the forum threads who share published research that relates to muscle growth. Most of the time, however, the information is based on hearsay or personal experiences. Weight lifters could have actually experienced the amazing muscle gains they describe. Other more plausible scenarios are:

• People who sell performance enhancing products log in under multiple usernames to promote their products.

• Forum posters may have inaccurate memories or exaggerate their strength gains.

• Some bodybuilders who post on the forums are genetically gifted.

• Some bodybuilders who post on the forums may use steroids.

• Some people on bodybuilding forums have just experienced a placebo effect.

This information isn’t meant to trash bodybuilding sites. Tim Ferriss says that bodybuilders are often on the forefront of testing out new medical findings. Instead of taking everything at face value, a better course of action is to:

1. Skim through the forums to find popular topics.

2. Then search PubMed for scientific evidence for any chemicals or supplements or training methods or endocrinological topics that get mentioned.

Three of my favorite ways of searching PubMed are:

1. using the title/abstract search

2. using the MeSH terms

3. limiting the search to studies in humans