Last week we quizzed our readers on traits associated with BMI among 23andMe’s customers. Congratulations to Suellen, the winner of the quiz! She got all three answers correct and will receive an Amazon gift card. So what were the correct answers? Read on&#8230;
Which physical trait is most associated with BMI? Shoe size.
<div style="margin-top: 15px; margin-bottom: 15px; border: 1px solid #ccc; width: 600px;"><img decoding="async" class="aligncenter size-large wp-image-12686" title="BMI-physical" src="https://blog-api.23andme.com/wp-content/uploads/2012/05/BMI-physical-1024x442.png" alt="" width="600" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/05/BMI-physical-1024x442.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2012/05/BMI-physical-300x130.png 300w, https://blogcms.23andme.com/wp-content/uploads/2012/05/BMI-physical-768x332.png 768w, https://blogcms.23andme.com/wp-content/uploads/2012/05/BMI-physical-880x380.png 880w, https://blogcms.23andme.com/wp-content/uploads/2012/05/BMI-physical-1180x510.png 1180w" sizes="(max-width: 1024px) 100vw, 1024px" /></div>
Shoe size is very strongly correlated with BMI in 23andMe’s database. For each standard deviation increase in shoe size, BMI increases by 1.18 units. Put another way, the BMI of the bottom fifth of the shoe size distribution is 3.21 units lower on average than that of the top fifth. This corresponds to a difference of about 20 lbs in people who are 5’8” tall.
We’re really not sure what to make out of this one. Shoe size is also correlated with height but when we factored height into the analysis shoe size was still the most strongly correlated trait. Anecdotally, people’s shoe sizes can increase or decrease with weight gain and loss. It’s possible that people with wider feet may compensate by increasing their shoe size instead of choosing a wider shoe of the same size, or perhaps shoe size is a proxy for body frame, and people with larger shoe sizes have “bigger bones”. Have a theory? Add it to the comments below.
Having a round face, low arches, upturned nose, and feet that point outwards are also associated with BMI but to a lesser extent.
Which food item is most associated with BMI? Diet soda.
<div style="margin-top: 15px; margin-bottom: 15px; border: 1px solid #ccc; width: 600px;"><img decoding="async" class="aligncenter size-large wp-image-12687" title="BMI-food" src="https://blog-api.23andme.com/wp-content/uploads/2012/05/BMI-food-1024x430.png" alt="" width="600" /></div>
The surprise for us here was that ice cream consumption was not really correlated with BMI at all. On the other hand, people who drink diet soda five or more times a day have an average BMI nearly 5 units higher than those who never drink diet soda. Not to imply that we should all trade in that diet coke for a double hot fudge sundae &#8212; we don’t know whether drinking soda is a cause, a consequence, or just linked to something else that causes weight gain. These findings do, however, parallel that of a study conducted in Texas, in which normal weight individuals were followed for 8 years. People who reported drinking more diet soda gained more weight over those 8 years, suggesting that diet soda might actually lead more directly to weight gain.(1) But for now, the jury’s still out.
Some other foods were associated with BMI, too, including red meat, yogurt, and vegetables.
Which personality or behavior trait is most associated with BMI? Activity and depression.
<div style="margin-top: 15px; margin-bottom: 15px; border: 1px solid #ccc; width: 600px;"><img decoding="async" class="aligncenter size-large wp-image-12688" title="BMI-personality" src="https://blog-api.23andme.com/wp-content/uploads/2012/05/BMI-personality-1024x549.png" alt="" width="600" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/05/BMI-personality-1024x549.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2012/05/BMI-personality-300x161.png 300w, https://blogcms.23andme.com/wp-content/uploads/2012/05/BMI-personality-768x412.png 768w, https://blogcms.23andme.com/wp-content/uploads/2012/05/BMI-personality-880x472.png 880w, https://blogcms.23andme.com/wp-content/uploads/2012/05/BMI-personality-1180x633.png 1180w" sizes="(max-width: 1024px) 100vw, 1024px" /></div>
These are less of a surprise. Activity is strongly correlated with BMI, and is no doubt due to the calorie burning benefits of exercise. The reverse may also be true &#8212; being overweight may itself decrease activity levels, creating a vicious cycle.
For depression, the arrow of causation seems to point in both directions. For example, a recent meta-analysis found that being overweight or obese increased the risk of developing depression, and having depression increased the risk of becoming obese.(2)
Having greater levels of self-discipline was correlated with lower BMI to a lesser extent, but aside from this we didn’t find a significant relationship between BMI and any other personality factors.
Check back soon for our next quiz and another chance to win!
(1)  Fowler, SP, Williams, K, Resendez, RG, Hunt, KJ, Hazuda, HP, &amp; Stern, MP. (2008). Fueling the Obesity Epidemic? Artificially Sweetened Beverage Use and Long-term Weight Gain. Epidemiology, 16(8): 1894-1900.
(2)  Luppino, FS, de Wit, LM, Bouvy, PF, Stijnen, T, Cuijpers, P, Penninx, BWJH, Zitman, FG (2010). Overweight, Obesity, and Depression: A systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010;67(3):220-229.

23andMe Blog

23andMe Blog Team

Quiz Answers: Traits Associated With BMI

<img decoding="async" class="alignright size-full wp-image-219" title="feetscale" src="https://blog-api.23andme.com/wp-content/uploads/2008/05/feetscale.jpg" alt="" width="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2008/05/feetscale.jpg 425w, https://blogcms.23andme.com/wp-content/uploads/2008/05/feetscale-300x199.jpg 300w" sizes="(max-width: 425px) 100vw, 425px" />
Besides height and weight, can you guess what feature is most strongly correlated with body mass index (BMI)? Over the next few months, we’ll be testing your knowledge of some of the most interesting associations we’re seeing in the 23andMe database. Guess right, and you could win cool prizes, including gift cards and 23andMe schwag! Then come back the next week to learn the answers and see who won.
This quiz is now closed. Read on to learn more about how we find these associations! 
 
What can we discover?
23andMe helps its customers connect with the latest research on correlations between genetic variations and health conditions and traits. These genetic variations could be pieces of the puzzle explaining why some people develop, say, type 2 diabetes, or why some people have curly hair.
With the help of our customers we’ve also made new discoveries of genetic associations for things like smelling the asparagus when you pee, Parkinson’s disease, and hypothyroidism. But you can explore correlations between practically anything, and 23andMe’s database, which so far has more than 150,000 genotyped customers contributing more than 40 million answers on hundreds of different topics, is a uniquely powerful platform for discovery.
What’s in a correlation?
<div style="border: 1px solid #ccc; width: 315px; padding: 10px; margin-left: 15px; background-color: #eee; font-size: 11px; float: right;">
Does correlation imply causation?
No. Correlation sometimes points to causes &#8212; cigarette smoke contributing directly to lung cancer is a common example &#8212; but it can often be due to some other underlying factor. For example, owning a house may be correlated with lower risk of type 2 diabetes*, but this doesn’t mean that home ownership protects you from having the disease. Instead, it could be that some other factor, such as higher socioeconomic status, makes it more likely that someone is able to buy a house as well as eat a healthier diet, which helps lower one’s risk for type 2 diabetes.
To avoid these sorts of “phantom” associations, researchers often add include demographic or other factors in their analyses to see if those factors explain away the findings. This is usually referred to as “controlling for” various factors.
* fictitious example
</div>
When we search for correlations, we’re looking to see whether there’s a relationship between two different variables, such as smoking and lung cancer. Sometimes we might investigate the relationship between two specific things, but often researchers will look at many different variables to see if any of them are correlated with the outcome of interest. In genetic associations, most studies routinely look at thousands or millions of genetic variants to find correlations with a trait or disease.
When we do this, we are essentially testing many different hypotheses at once. Each variable that you investigate gives you another chance to find a correlation, but if you find one, is it because it’s a real correlation, or simply because you looked at so many variables that one of them just happened to work? We can calculate statistics to measure how likely it is for a finding to be due to chance (also called “statistical significance”), and adjust these statistics based on how many different things we’re testing. After all that’s said and done, the less likely it is that a finding is due to chance, the more likely it is to represent a real association.
More than genetics
Because 23andMe looks at numerous traits as well as genetics, we can explore not just whether genetic factors are correlated with traits, but whether different traits are correlated with each other. For example, we’ve tested BMI against approximately 1000 different traits, habits, and conditions reported by our customers. What we found might surprise you&#8230;
<a title="Quiz Answers: Traits Associated With BMI" href="https://blog.23andme.com/23andme-research/bmi-quiz-answers/">Check out this post to see what we discovered!</a>

What Do Diet and Personality Have to Do With BMI?

<img loading="lazy" decoding="async" class="wp-image-11716 size-full alignright" src="http://35.88.189.111/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud.png" alt="" width="1496" height="692" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud.png 1496w, https://blogcms.23andme.com/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud-300x139.png 300w, https://blogcms.23andme.com/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud-768x355.png 768w, https://blogcms.23andme.com/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud-1024x474.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud-880x407.png 880w, https://blogcms.23andme.com/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud-1180x546.png 1180w" sizes="auto, (max-width: 1496px) 100vw, 1496px" />
Like many people around the world, the health content team at 23andMe rang in 2012 with resolutions of staying healthy and it seemed fitting to delve into the genetics underlying response to diet and exercise, eating behavior and cholesterol levels. As we eased in to the new year, we segued into reproduction, updating our existing reports on male infertility and gestational diabetes, and we also recently added new genetic associations for tuberculosis susceptibility, Hodgkin lymphoma, and atopic dermatitis.
In the end of February we paid tribute to rare diseases by celebrating <a href="../2012/02/29/did-you-know-its-not-so-rare-to-have-a-rare-disease/" target="_blank" rel="noopener">Rare Disease Day</a> and putting out new reports for <a href="https://www.23andme.com/sarcoma/" target="_blank" rel="noopener">sarcoma</a> and <a href="https://www.23andme.com/mpn/" target="_blank" rel="noopener">myeloproliferative neoplasms (MPN)</a> –  rare cancers that we are particularly passionate about as evidenced by our <a href="../2012/02/27/weve-come-a-long-long-way-together-but-were-not-there-yet/" target="_blank" rel="noopener">innovative research efforts</a> for these conditions.
Read more about some of our new and updated reports…
<h6>Tying genetics to diet and exercise</h6>
Does exercise help you lose weight or does it barely seem to make a difference? Have you ever wondered why some people who eat a lot of fatty foods don’t gain weight while others seem to pack on the pounds? Our Response to Exercise and Response to Diet reports may provide insight into the genetics underlying these complex topics that are already known to be strongly influenced by behavior and environment. Similarly, if you tend to reach for second helpings, our report on eating behavior may also shed some light!
<h6>Insight into your cholesterol</h6>
Have you ever wondered why your LDL cholesterol level is naturally low or why it seems to stay high despite your best efforts to lower it? Towards the end of January we added a new report for LDL cholesterol – the “bad” cholesterol that is associated with heart disease – and updated our report on HDL cholesterol, which is the “good” cholesterol that is considered protective against heart disease. These reports may offer some clues for you,  but it’s important to keep in mind that the genetic landscape of cholesterol levels is highly complex and that lifestyle also plays a big role.
<h6>Genetic findings on reproductive health in Asians!</h6>
Sexual reproduction is what keeps the human species going, but from getting pregnant to having a healthy child, it doesn’t always work like a well-oiled machine. Approximately 15% of couples experience difficulties getting pregnant and <a href="../2012/02/06/snpwatch-genetic-variants-linked-to-male-infertility-in-asians/" target="_blank" rel="noopener">about half of these cases</a> are due to male infertility. We’ve updated our Male Infertility report to include genetic variants that influence sperm count in Asian men. In February we also added new findings for Asian women to our report on gestational diabetes, a pregnancy complication with symptoms similar to type 2 diabetes that affects about 3-5% of pregnant women.
<h6>Revving up reports for rare diseases</h6>
In the United States, a disease is defined as “rare” if it affects<a href="http://rarediseaseday.us/about/" target="_blank" rel="noopener"> fewer than 200,000 individuals</a>, or roughly one in 1500. Sarcoma and myeloproliferative neoplasms (MPN) fall into this category and in early March we added new reports for both of these rare cancers. Although these reports are considered “preliminary research” findings, mainly because they were generated with relatively small study groups, they are still exciting progress in research on these rare disorders.
23andMe customers can find more details on these and other conditions in their accounts. Not a member? <a href="https://www.23andme.com/store" target="_blank" rel="noopener">Visit our store</a>, or set up a<a href="https://www.23andme.com/user/signup/" target="_blank" rel="noopener"> free trial account</a> to browse these and other reports.

Health Watch: New Year’s Resolutions, Reproduction and Rare Diseases

<img loading="lazy" decoding="async" class="alignnone size-medium wp-image-10396" src="https://blog-api.23andme.com/wp-content/uploads/2011/11/foodchoicesna-300x220.jpg" alt="" width="300" height="220" srcset="https://blogcms.23andme.com/wp-content/uploads/2011/11/foodchoicesna-300x220.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2011/11/foodchoicesna.jpg 350w" sizes="auto, (max-width: 300px) 100vw, 300px" />
For some, eating a <a href="http://www.livestrong.com/article/86638-nutrition-information-donuts/" target="_blank" rel="noopener noreferrer">doughnut</a> every morning is a recipe for heart attack. For others, the doughnut doesn’t seem to matter–it’s almost as if certain individuals can’t get heart disease even if they try.
 The flip side is that people who are predisposed to heart disease can make lifestyle changes, in this example by cutting down on saturated fats and cholesterol, to decrease their odds of actually experiencing a heart attack. This is because heart disease is caused by a combination of genetic and lifestyle factors like diet and exercise. 
<h6>Genetics and Lifestyle</h6>
As a new paper published last month in <a href="https://www.google.com/url?q=http%3A%2F%2Fwww.plosmedicine.org%2Farticle%2Finfo%253Adoi%252F10.1371%252Fjournal.pmed.1001106&amp;sa=D&amp;sntz=1&amp;usg=AFQjCNG9EjWWh8juy6M7I8g_EpUd-zuN2A" target="_blank" rel="noopener noreferrer">PLoS Medicine</a> illustrates, lifestyle choices can have an even greater impact on heart disease risk depending on a person’s genetics. The study’s findings suggest that diet influences the association between SNPs in the 9p21 region of the genome and risk for heart attack and cardiovascular disease. 
The 9p21 region is one of the most established genetic associations for heart disease, but until now its interactions with environmental factors had not been thoroughly investigated. The current study, conducted by Ron Do of McGill University and the INTERHEART consortium, was carried out with DNA from over 27,000 people of different ethnicities.
A number of <a href="http://www.sciencemag.org/content/316/5830/1491.short" target="_blank" rel="noopener noreferrer">studies</a> have shown that one variants puts you at 1.5 higher odds of having a heart attack. In the current study, people with this variant who occasionally ate raw vegetables and fruit had a two-fold higher risk of heart attack compared to controls with a different variant who ate a similar diet. The surprising finding is that people the higher risk variant who frequently ate raw vegetables and fruit did not experience heart attacks more than controls.
<h6>Ethnicity Matters Too</h6>
The effect of diet on the association between SNPs in the 9p21 region and heart attack risk was strongest for people of South Asian ancestry. The evidence for this effect was suggestive but weaker in the European, Latin American, and Chinese populations studied. Although the researchers also looked to see if smoking and exercise modified the relationship between 9p21 SNPs and heart attack risk, they didn’t find evidence of a connection. 
These findings suggest that people with a predisposition for coronary heart disease, at least based on their genotype at 9p21, can eat a <a href="http://www.mayoclinic.com/health/heart-healthy-diet/NU00196" target="_blank" rel="noopener noreferrer">heart-healthy diet</a> to decrease their chances of actually experiencing a heart attack. Thus, having two risky versions of these SNPs isn’t necessarily a recipe for heart attack. We already know that diet strongly impacts health–indeed there is a reason why your parents told you to eat your vegetables–and this study suggests that diet may actually override genetic risk in some cases.

Eating Veggies Can Decrease Genetic Risk for Heart Attack

<img decoding="async" class="alignright size-full wp-image-219" title="feetscale" src="https://blog-api.23andme.com/wp-content/uploads/2008/05/feetscale.jpg" alt="feetscale" width="350" srcset="https://blogcms.23andme.com/wp-content/uploads/2008/05/feetscale.jpg 425w, https://blogcms.23andme.com/wp-content/uploads/2008/05/feetscale-300x199.jpg 300w" sizes="(max-width: 425px) 100vw, 425px" />
We all know people struggling with weight issues. Maybe they’re overweight and can’t seem to lose the pounds no matter what new diet or exercise regime they try. Or, maybe they’re underweight and have a hard time bulking up no matter how many donuts they consume or weights they lift. Clearly, there’s more to your weight than what you eat.
Researchers have been hot on the trail of genetic factors influencing obesity ever since the <a href="http://www.hhmi.org/genesweshare/d130.html">discovery of the gene coding for leptin</a>, a protein responsible for telling the brain “I’m full.” But just having a genetic variant linked to obesity doesn’t mean stretchy waist pants are a certainty — many factors interact with diet to affect your health.
Several years ago, a team led by Dolores Corella and Jose Ordovas discovered that the variant in the APOA2 gene is <a href="http://www.clinchem.org/cgi/content/full/53/6/1144">associated with obesity</a> as well as general food measures like total calorie and protein intake. In a new study published last month in the <a href="http://archinte.ama-assn.org/cgi/content/abstract/169/20/1897">Archives of Internal Medicine</a>, Corella and Ordovas replicated the association with obesity in three independent populations  and determined that the association depends specifically on the amount of saturated fat in the diet. More than 3400 individuals across three population groups — 2532 people of European ancestry and 930 Hispanics from Puerto Rico — participated in the study, providing data on dietary intake, physical activity, body mass index (BMI) and other variables.
In the two European populations, individuals with two copies of the C version of had significantly higher calorie intake than individuals with at least one copy of the T version  — a finding that echoed their previous work. When Corella and her colleagues looked at BMI, however, they found that was significantly associated with higher BMI, but only in individuals who consumed high amounts of saturated fat, irrespective of total calorie intake.
In all three populations, there was no association between genotype and BMI in individuals who consumed diets low in saturated fat. Furthermore, there was no significant difference in BMI for individuals who had low intake and individuals who had high intake if they had at least one copy of the T version. But people with the CC genotype who consumed diets high in saturated fat had significantly higher BMI than people with either the TC or TT genotype who also consumed high saturated fat diets. After combining data from the three groups, Corella’s team determined that individuals with the CC genotype who had high saturated fat intake also had about 1.8 times higher odds of obesity than individuals with the T version  who consumed similar amounts of saturated fat, total calorie intake being equal.
Although earlier research in animals has implicated APOA2 in obesity, its role in human health has been controversial. In this study, Corella and her team show that saturated fat intake can interact with a genetic variant in APOA2 to increase obesity risk. In fact, the variant makes more of a difference the more saturated fat one consumes. While minimizing saturated fat intake continues to be common sense, in a society characterized by rich diets and increasingly sedentary lifestyles, discoveries like this drive home the fact that genetics and environment together form an intricately interwoven picture of our health.
(Many thanks to TRK for bringing this study to our attention!)

Do These Genes Make Me Look Fat? It Depends on What You Eat

<img loading="lazy" decoding="async" class="alignright size-full wp-image-2810" title="yogurtgirl" src="https://blog-api.23andme.com/wp-content/uploads/2009/02/yogurtgirl.jpg" alt="" width="350" height="232" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/02/yogurtgirl.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2009/02/yogurtgirl-300x199.jpg 300w" sizes="auto, (max-width: 350px) 100vw, 350px" />
Generally when you think about what separates humans from other species, features like upright walking, large brains and language come to mind.
But diet has actually played an enormous role in human evolution. Today at the annual meeting of the <a href="http://www.aaas.org" target="_blank" rel="noopener">American Association for the Advancement of Science</a>, a panel of anthropologists, geneticists and paleontologists got together to discuss how who we are has been shaped by what we eat.
Perhaps the most surprising conclusion was that – despite what some diet gurus may say – there is no &#8220;natural&#8221; human diet. Not only can humans thrive on a wide variety of diets, from the highly carnivorous fare of nomadic Siberians to the virtually all-potato menu consumed by native Peruvians, but thanks to evolution our species can change its diet surprisingly readily.
&#8220;You can find humans living well and healthily from a tremendous diversity of diets,&#8221; said William Leonard, an anthropologist at <a href="http://www.northwestern.edu/newscenter/stories/2009/02/leonard.html" target="_blank" rel="noopener">Northwestern University</a> in Evanston, Ill.
But all cultures have one dietary feature in common, said Harvard University primatologist Richard Wrangham – they cook their food. Wrangham believes the advent of cooking during human prehistory was a major evolutionary milestone, because it essentially pre-digested starches and proteins and softened food, helping increase the amount of energy that could be extracted on it. In fact, he pointed out that people in modern technological societies who take up so-called &#8220;raw food&#8221; diets usually lose substantial amounts of weight.
Many diet books advise following a high-protein, low-carbohydrate diet in order to emulate the eating habits of pre-agricultural humans. Whatever the benefits of such a diet, however, it is clear that in the 10,000 years since the development of farming our genes have responded to the increasing availability of foods such as rice, grains and milk.
&#8220;I would say most people who descend from agricultural populations are actually pretty well adapted to a starch diet, because most of the world eats a lot of rice, a lot of corn and a lot of potatoes, said Anne Stone, a geneticist at Arizona State University.
Stone and her colleagues have studied the gene AMY1, which encodes a salivary protein called amylase that breaks down starch. All people have multiple copies of the AMY1 genes. But those from traditionally agricultural populations, such as the Japanese and Europeans, have many more than those from cultures that have never practiced agriculture.
Customers of 23andMe may be able to see the evolutionary effects of an agricultural heritage in their own genetic data. Before people started herding cattle, goats and sheep, the human biological machinery for digesting milk was turned off not long after infancy – perhaps to prevent older children from getting in destructive fights over breast milk. But with herd animals on the scene, when a genetic modification that kept milk digestion functioning into adulthood arose in Europe around 8,000 years ago, it was so beneficial that it eventually spread throughout the continent.
23andMe customers have one modified version of the lactase gene for each A at the SNP rs4988235.
Similar scenarios happened in several other parts of the world as well, so that now many people of European and some of African ancestry can easily digest large amounts of milk.

The Most Natural Human Diet: Just About Anything

Last week in the Blog we reported on a new study that identified an interesting genetic trade-off – a genetic variant known that has one effect on a person&#8217;s vulnerability to malaria, and the opposite on susceptibility to HIV infection. The &#8220;Duffy negative&#8221; version of the gene, which is common among Africans and African Americans, appears to protect a person against malaria but increases vulnerability to infection by HIV. As it turns out, Duffy is not the only example of a genetic trade-off in humans.   There are many instances of genetic variation throughout the human genome that offer both genetic advantages and disadvantages to their carriers.  
<h6> Sickle Cell Anemia vs. Malaria</h6>
<a href="https://www.23andme.com/topics/carrier/sickle-cell-anemia">Sickle cell anemia</a> is caused by a genetic mutation that alters the shape of an individual’s red blood cells.   This mutation, called Hbs, causes red blood cells to take on a sickle-shape, as opposed to the normal round shape.   The sickle-shaped cells then get stuck in the veins and arteries, causing tremendous pain and discomfort.   Sickle cell anemia is recessively inherited, meaning that someone must inherit the Hbs mutation from both parents in order to have the disease. Malaria is a disease that kills between 1 and 3 million people worldwide each year, mainly in the tropics.   After scientists noticed similarities between the geographic distribution of sickle cell anemia and malaria, they began to wonder if there was some sort of connection between the two.
Experiments soon confirmed that sickle cell anemia is a sort of genetic Faustian bargain. Recall that individuals with two copies of Hbs suffer from sickle cell anemia, but people with only one copy of the mutation do not.   They do however, display a resistance to malaria compared with people who have no copies of Hbs.   Occasionally, a pair of malaria-resistant parents will both pass Hbs – and thus sickle cell anemia – to their child. But overall, having only one copy improved the survival rate in human history so much that the Hbs mutation continues to exist in in spite of the disease burden it causes.
<h6>Hereditary Hemochromatosis vs. Iron Deficiency</h6>
Hereditary hemochromatosis (HH) is a genetic condition in which the body absorbs too much iron from the diet.   This leads to the toxic build-up of iron in the tissues of major organs such as the liver and heart.   Without treatment, HH can lead to organ failure. Genetic studies have found that HH, like sickle-cell, is a recessive trait. It appears to have evolved about 1,400 years ago, probably in western Europe, at a time when people ate mostly cereal grains – which are very low in iron. Because having some amount of iron in the diet is essential to maintain normal body functions, this was a serious problem.   During this time period, the ability to store extra iron in the body would have been helpful.   Individuals with HH could take iron from foods when it was available, and then store it in the organ tissues, dipping into those reserves when the supply of iron-rich foods was low.   Today, however, iron is much more abundant. It is an excess of iron, not a lack of it, that threatens the health of people with HH.
<h6>The Paleolithic Diet vs. Obesity</h6>
Why is it that humans crave the very foods that are unhealthy?   Why do we prefer donuts and candy to celery and spinach?   Like hereditary hemochromatosis, the source of this cruel irony lies in the history of our species. The human brain is a very expensive organ to maintain.   It requires a lot of energy to keep all the synapses working correctly, and simply feasting on celery would not do the trick.   Hundreds of thousands of years ago, our ancestors began eating meat as a way to get the required energy their brains needed.   Meat is high in the energy that humans needed to survive, and also in long-chain polyunsaturated fats, which are essential to maintenance of brain tissue.   Bone marrow, the fatty substance inside long bones, is also high in fat and calories, and was thus another prized item in our ancestors’ early diet.   Because foods high in fat and calories were so important to our ancestors, they would have searched them out and evolved a natural preference for them.   Their bodies would have evolved to store any excess fat, in case there were was a long hiatus until the next piece of meat or bone marrow came their way.   This ‘thrifty’ metabolic approach to fat has persisted to the present day, despite drastic changes in the way we feed ourselves.   Now, instead of searching constantly for food we have seemingly unlimited access to Twinkies, beer and other high-calorie delights.   But our bodies are still storing the excess fat. The genetics of obesity are complicated, and by no means can they be fully explained by our ancestors’ diet. But the dramatic change in the human diet since the Stone Age does help explain our cravings from an evolutionary perspective. Variations in the human genome are full of examples such as these: genetic mutations that are beneficial in some ways but harmful in others, or that used to be beneficial, but now result in an increased waistline.   Understanding these genetic ‘trade-offs’ is helpful to understanding the history of the human genome, and could be helpful in tackling conditions such as sickle-cell anemia, hereditary hemochromatosis, obesity and many others.

diet — Page 3