Category: Medicine

Vaccination, and social information networks

By Razib Khan | November 12, 2013 3:34 am

Preventable

If you have not read Julia Ioffe’s story about getting whooping cough at the age of 31 (also see follow up), you might want to. Here’s some further context, Vaccine Refusals Fueled California’s Whooping Cough Epidemic. This topic has been covered and dissected in great detail by many writers and scientists, so I won’t repeat what you already know in regards to herd immunity. There’s no point in preaching to the choir.

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CATEGORIZED UNDER: Medicine

Your health is your health

By Razib Khan | March 7, 2013 3:57 pm

A quick personal story. I have a treatable autosomal dominant condition. For the non-geneticists, that means any of my children have a 50% chance of exhibiting the trait. Even aggressive treatment is not usually initiated until one is in elementary school. But we want to know now, just so we can know (we plan to have more children soon, so we want to anticipate medical expenses or lack thereof, and well, just to know). When my wife went to the doctor today for a routine checkup for my daughter she asked for a blood test to confirm that my daughter exhibited, or did not, exhibit the symptoms (this is not a common SNP for what it’s worth).

Though the doctor was skeptical of the effectiveness of the test at this age, she also (according to my wife) decided to give my wife a lecture on the appropriateness of testing. Here’s what my wife emailed me:

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CATEGORIZED UNDER: Medicine
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None dare call it eugenics!

By Razib Khan | April 16, 2012 9:37 pm

Well, almost no one:

“The unspoken central reason for the societal taboo and the penal ban on incest is the possibility of hereditary defects — a factor that Strasbourg only hinted at. But the intention behind the eugenic argument is one that is indefensible, and not just in Germany with its terrible Nazi past: The increased risk of hereditary defects does not justify a legal ban. Otherwise you would have to legally ban other risk groups, like women over 40 or people with genetic diseases, from having children. Does anyone truly want to prevent predictable disabilities using penal measures and thus deny disabled children the right to life in 2012? That’s absurd. And yet such fears of genetic damage are precisely what shape the punishibility of sexual intercourse between siblings.”


There are a set of arguments against near relation incest which strike me as generally ad hoc. And there’s social science to back that up. Incest is reflexively disgusting to most people (depending on how it is categorized). But disgust alone is not a sufficient grounds for banning a practice in educated circles today, so people create rationales after the fact. David Hume would not be surprised.

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CATEGORIZED UNDER: Human Genetics, Medicine
MORE ABOUT: Genetics, Medicine

Doctors and life expectacy

By Razib Khan | April 8, 2012 5:18 pm

A friend pointed me to the following infographic on the concentration of doctors per county. The orange represents “very high need,” and dark blue “very low need.”

Now let’s compare it to life expectancy by county:

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CATEGORIZED UNDER: Medicine
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"Doctors don't cure nothing"

By Razib Khan | January 1, 2012 2:00 pm

NSFW


As I observed before, modern medicine is subject to some of the same statistical issues as social science in its tendency to put unwarranted spotlight on preferred false positive results. Trials and Errors – Why Science Is Failing Us:

This doesn’t mean that nothing can be known or that every causal story is equally problematic. Some explanations clearly work better than others, which is why, thanks largely to improvements in public health, the average lifespan in the developed world continues to increase. (According to the Centers for Disease Control and Prevention, things like clean water and improved sanitation—and not necessarily advances in medical technology—accounted for at least 25 of the more than 30 years added to the lifespan of Americans during the 20th century.) Although our reliance on statistical correlations has strict constraints—which limit modern research—those correlations have still managed to identify many essential risk factors, such as smoking and bad diets.

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CATEGORIZED UNDER: Culture, Medicine

Eggs: quantity and quality

By Razib Khan | December 30, 2011 3:05 am

In my post below on selection for the “better” zygote Michelle observes that “This would be relatively easy for the father, not so much for the mother.” I took her to mean either of two things,

1) Extraction of eggs is a major surgical affair. Extraction of sperm is not.

2) Males generally have many more sperm to contribute than females.

The latter issue made me go look for data on human females, by age. The paper A systematic review of tests predicting ovarian reserve and IVF outcome had what I was looking for. First, let’s review the cumulative distribution of fertility curves for women:

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CATEGORIZED UNDER: Medicine
MORE ABOUT: Fertility

Promiscuity and vaginal bacterial diversity

By Razib Khan | December 17, 2011 10:10 am

It’s a fun fact that there are an order of magnitude more bacterial cells in your body than your own cells. Not only that, it’s well known that we wouldn’t flourish, let alone survive, without our gut “flora,” which digest material which would otherwise pass through out system. Not only are microbes good for us, but they’re also bad for us. The evolutionary flexibility of microbial pathogens is one of the major arguments for why sex exists among multiceullar species: it allows them to adapt to rapidly fluctuating disease pressures. Therefore, obviously the ecology of multicellular organisms’ microbial flora is essential to properly characterize. One element of the project involves genomics. This is not so easy for microbes because we don’t have the reference sequences of most of these organisms. We rely mostly on species which are easy to culture, and that does not include most lineages in the wild. That being said, there are workarounds, such as looking at the 16S rNA sequence, which is strongly constrained in bacterial lineages (i.e., it can serve as a “clock” to measure divergence of very deeply separated lineages).

With that, a new paper, Promiscuity in mice is associated with increased vaginal bacterial diversity:

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CATEGORIZED UNDER: Anthroplogy, Genomics, Medicine

Up with nurses! Down with doctorates!

By Razib Khan | October 1, 2011 1:48 pm

In light of growing health care costs and the demographic reality of an aging profession stories like this one in The New York Times are both depressing and hopeful. Calling the Nurse ‘Doctor,’ a Title Physicians Oppose:

But while all physician organizations support the idea of teamwork, not all physicians are willing to surrender the traditional understanding that they should be the ones to lead the team. Their training is so extensive, physicians argue, that they alone should diagnose illnesses. Nurses respond that they are perfectly capable of recognizing a vast majority of patient problems, and they have the studies to prove it. The battle over the title “doctor” is in many ways a proxy for this larger struggle.

Six to eight years of collegiate and graduate education generally earn pharmacists, physical therapists and nurses the right to call themselves “doctors,” compared with nearly twice that many years of training for most physicians. For decades, a bachelor’s degree was all that was required to become a pharmacist. That changed in 2004 when a doctorate replaced the bachelor’s degree as the minimum needed to practice. Physical therapists once needed only bachelor’s degrees, too, but the profession will require doctorates of all students by 2015 — the same year that nursing leaders intend to require doctorates of all those becoming nurse practitioners.

Nursing is filled with multiple specialties requiring varying levels of education, from a high school equivalency degree for nursing assistants to a master’s degree for nurse practitioners. Those wishing to become nurse anesthetists will soon be required to earn doctorates, but otherwise there are presently no practical or clinical differences between nurses who earn master’s degrees and those who get doctorates.

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CATEGORIZED UNDER: Medicine
MORE ABOUT: Medicine

Getting better sperm donors

By Razib Khan | August 15, 2011 11:53 pm

The British newspapers have been reporting on a bizarre story about a Dutch sperm donor who hid a history of mental problems from recipients. I didn’t pay much attention to it because of the British tabloid media’s tendency to sensationalize. But Radio Netherlands also reported the outlines of the story, and there seems to be validity to the broad facts at hand. A Dutch man with a history of mental illness did father many children by offering his services online, and hiding various conditions from potential mothers. Now several of the children have developed the same problems (e.g., autism).

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CATEGORIZED UNDER: Genetics, Medicine
MORE ABOUT: Sperm donors

Crohn's disease is about barely keeping you alive

By Razib Khan | August 10, 2011 1:05 am

The Pith: Natural selection is a quick & dirty operator. When subject to novel environments it can react rapidly, bringing both the good and the bad. The key toward successful adaptation is not perfection, but being better than the alternatives. This may mean that many contemporary diseases are side effects of past evolutionary genetic compromises.

The above is a figure from a recent paper which just came out in Molecular Biology and Evolution, Crohn’s disease and genetic hitchhiking at IBD5. You probably have heard about Crohn’s disease before, there are hundreds of thousands of Americans afflicted with it. It’s an inflammatory bowel ailment, and it can be debilitating even to very young people. The prevalence also varies quite a bit by population. Why? It could be something in the environment (e.g., different diet) or genetic predisposition, or some combination. What the figure above purports to illustrate is the correlation between Crohn’s disease and the expansion of the agricultural lifestyle.

But don’t get overexcited Paleos! There are many moving parts to this story, and I need to back up to the beginning. The tens of thousands of genes which you inherited from your parents are embedded within the genome and aligned in a set of sequences, one after the other. On the one hand for the purposes of conceptualizing evolutionary dynamics, such as natural selection or random genetic drift, focusing on a single gene is useful. It has power to illustrate some basic and elementary principles.  But sometimes you need to take a more synoptic view, and look at genes in their broader context. In this post I’ll avoid molecular or statistical epistasis, gene-gene interaction. Rather, let’s just consider the static landscape of the genome, where genes are physical concrete entities which are embedded in a particular spatial relationship to other genes, upstream or downstream in the genetic code. These physical or statistical associations of genes can form a de facto supergene through linkage, and their variants combine to form haplotypes, sequences of markers across small stretches of the genome. But recall that these associations are counter-balanced by genetic recombination, which tears apart physical sequences and sows them to the opposite DNA strand.

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Dominance, the social construct that confuses

By Razib Khan | July 25, 2011 1:31 pm

A story in The Los Angeles Times seems to point medical implications of being a sickle cell carrier, Sickle cell trait: The silent killer:

At least 17 high school and college athletes’ deaths have been tied to sickle cell trait during the past 11 years. The group includes Olivier Louis, a player at Wekiva High School near Orlando, who died on Sept. 7, 2010, following his first football practice.

You have surely heard about sickle cell anemia. It is a recessive disease which expresses in those who carry two sickle cell alleles. T-boz of TLC has the disease for example due to her homozygosity. But the allele also famously confers some resistance against malaria, which explains its concentration in regions which have historically been malarial. Sickle cell is arguable the classic case of heterozygote advantage driving the emergence of a recessive disease. The frequency of the allele is balanced at the equipoise between the proportion of people who are more susceptible to malaria if its proportion is too low and those who express sickle cell anemia if its proportion is too high. This advantage is obviously context sensitive. The standard assumption is that in a non-malarial environment selection pressure against anemia will drive the frequency of the allele down over time as heterozygotes don’t impose a floor in the proportion of the mutant allele. This seems to have occurred among African Americans, they’re ~80% West African, but their frequency of the sickle cell anemia allele is less than {0.80*(the West African proportion)} from what I know (remember that the median number of generations which an African American’s black ancestors have been in the USA is probably ~10).

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CATEGORIZED UNDER: Genetics, Health, Medicine

Bacteria tell the tale of human intercourse

By Razib Khan | July 20, 2011 1:39 am

The Pith: the genetic relationships between bacteria in our stomach can tell us a lot about the relationships between various groups of people. Additionally, the distribution of different strains of bacteria may have significant public health implications.

The above image is from a paper which was pushed online yesterday in PLoS ONE: Evolutionary History of Helicobacter pylori Sequences Reflect Past Human Migrations in Southeast Asia. It’s a paper which caught my attention for several reasons. First, I’ve exhibited some curiosity about the history and prehistory of Southeast Asia of late. Elucidating this region’s historical dynamics may bear upon more general questions of human evolutionary and cultural process. Second, H. pylori is a fascinating organism whose connection to specific human populations is tight enough that it can shed light on past interactions of different groups. In short, just like humans H. pylori exhibits regional specificity and local history. But additionally, H. pylori is also subject to natural selection after introduction into a new population, and so can serve as a window upon cultural contacts which might otherwise leave a light demographic footprint. In other words, the spread of H. pylori across human populations may be compared to the spread of Buddhism. This religion came to China and Japan with some Buddhists of South and Central Asian origin, but by and large its spread was memetic rather than through natural increase of a Buddhist population.

First, let’s hit the abstract:

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CATEGORIZED UNDER: Anthroplogy, Genetics, Medicine

You are a mutant!

By Razib Khan | June 12, 2011 3:36 pm

ResearchBlogging.org
The Pith: You are expected to have 30 new mutations which differentiate you from your parents. But, there is wiggle room around this number, and you may have more or less. This number may vary across siblings, and explain differences across siblings. Additionally, previously used estimates of mutation rates which may have been too high by a factor of 2. This may push the “last common ancestor” of many human and human-related lineages back by a factor of 2 in terms of time.

There’s a new letter in Nature Genetics on de novo mutations in humans which is sending the headline writers in the press into a natural frenzy trying to “hook” the results into the X-Men franchise. I implicitly assume most people understand that they all have new genetic mutations specific and identifiable to them. The important issue in relation to “mutants” as commonly understood is that they have salient identifiable phenotypes, not that they have subtle genetic variants which are invisible to us. Another implicit aspect is that phenotypes are an accurate signal or representation of high underlying mutational load. In other words, if you can see that someone is weird in their traits, presumably they are rather strange in their underlying genetics. This is the logic behind models which assume that mutational load has correlates with intelligence or beauty, and these naturally tie back into evolutionary rationales for human aesthetic preferences (e.g., “good genes” models of sexual selection).

Variation in genome-wide mutation rates within and between human families:

J.B.S. Haldane proposed in 1947 that the male germline may be more mutagenic than the female germline…Diverse studies have supported Haldane’s contention of a higher average mutation rate in the male germline in a variety of mammals, including humans…Here we present, to our knowledge, the first direct comparative analysis of male and female germline mutation rates from the complete genome sequences of two parent-offspring trios. Through extensive validation, we identified 49 and 35 germline de novo mutations (DNMs) in two trio offspring, as well as 1,586 non-germline DNMs arising either somatically or in the cell lines from which the DNA was derived. Most strikingly, in one family, we observed that 92% of germline DNMs were from the paternal germline, whereas, in contrast, in the other family, 64% of DNMs were from the maternal germline. These observations suggest considerable variation in mutation rates within and between families.

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Fair & balanced on circumsion

By Razib Khan | April 4, 2011 11:48 am

When Michelle mentioned on Twitter that she was going to write about circumcision, I told her to expect some angry people to come out of the wood-work. Today she has a post up at Scientific American, What’s the deal with male circumcision and female cervical cancer? She concludes:

In addition, while it is true that women with circumcised partners are less likely to get cervical cancer, they are not immune. Women with circumcised partners still contract HPV and develop cervical cancer! They just do it at a reduced rate.

There are other methods that are much more likely to reduce a woman’s chance of contracting HPV and developing cervical cancer, such as vaccination and condom use. Therefore, from a public health standpoint in the United States, it may not be necessary to circumcise male babies solely for the purpose of reducing the risk of cervical cancer in his future sexual partners (of course, this doesn’t take into account the possibility that the child might not be heterosexual).

On the whole I think that Michelle’s take is reasonable and fair-minded. But, I think numbers are of the essence here. What is the expected reduction in rate of risk? This was the major bone I had to pick with Jesse Bering’s post on this topic last year at Scientific American. Bering closes on a pro-circumcision note on public health grounds:

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CATEGORIZED UNDER: Health, Medicine
MORE ABOUT: Circumcision

Who are those Houston Gujus?

By Razib Khan | February 14, 2011 3:38 pm

The figure to the left is a three dimensional representation of principal components 1, 2, and 3, generated from a sample of Gujaratis from Houston, and Chinese from Denver. When these two populations are pooled together the Chinese form a very homogeneous cluster. They don’t vary much across the three top explanatory dimensions of genetic variance. In contrast, the Gujaratis do vary. This is not surprising. In the supplements of Reconstructing Indian population history it was notable that the Gujaratis did tend to shake out into two distinct clusters in the PCAs. This is a finding you see over and over when you manipulate the HapMap Gujarati data set. In reality, there aren’t two equivalent clusters. Rather, there’s one “tight” cluster, which I will label “Gujarati_B” from now on in my data set, and another cluster, “Gujarati_A,” which really just consists of all the individuals who are outside of Gujarati_B cluster. Even when compared to other South Asian populations these two distinct categories persist in the HapMap Gujaratis.

Zack has already identified a major difference between the two clusters: Gujarat_A has some individuals with much more “West Eurasian” ancestry. To be more formal about this in the future I simply assigned individuals in my merged data set to one of the two Gujarati clusters based on their position in the first two PCs. Yesterday night I ran ADMIXTURE K = 2 to 10, with 75,000 SNPs. I also removed the Native American groups, and added more European and East Asian samples from the HapMap. Below are some populations at K = 4:

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Does your twin have "rights" on your genomes?

By Razib Khan | February 3, 2011 8:08 pm

Randall Parker asks, Genetic Privacy And Identical Twins:

Suppose you have a right to genetic privacy. You might believe you do. Suppose you have an identical twin. Suppose the identical twin decides to publish his (or her) genetic sequence on the web. Do you have the right to stop this?

People who have identical genetic sequences each can get themselves sequenced and then release their genetic data for all the world to download and study. But when an identical twin does this another person also gets their genetic sequence released to the world.

So should twins be able to legally stop each other from publishing their shared DNA sequence on the web?

This is not a question that just applies to twins. As I noted earlier individuals share ~50% of their distinctive genetic material with their parents and full-siblings. I share ~12.5% with first cousins whom I have never met. If I just released my raw sequence by uploading it somewhere I would implicitly “expose” to a non-trivial degree dozens of people (many without their knowledge).

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One diabetes gene to explain it all?

By Razib Khan | December 7, 2010 12:01 pm

372px-PresidentTaftTelephoneCrop
President William Howard Taft

It is the best of times, it is the worse of times. On the one hand the medical consequences of human genomics have been underwhelming. This is important because this is the ultimate reason that much of the basic research is funded. And yet we’ve learned so much. The genetic architecture of skin color has been elucidated, and we’ve seen a clarification of patterns of natural selection in the human genome. The finding last spring of Neandertal admixture in modern human populations is perhaps the most awesome pure science finding of late, coming close to resolving a decades old debate in anthropology. This doesn’t cure cancer, but it does connect the dots about the human past, and that’s not trivial. We are species haunted by our memories, so we might as well get them right!

But all hope is not lost. Research continues. And one area which general surveys of genomic variation have usually shown to be targets of natural selection, and, also have clear and immediate biomedical relevance, is that of metabolism. How we eat, and how we process and integrate the food we eat, is of obvious fitness relevance in the evolutionary and medical senses. It turns out that there is even variation in our saliva which is probably due to natural selection. The combination of diversity in human cuisine and susceptibility to the diseases of modern life indicate possibilities as to the relationship between past selection pressures and contemporary patterns of genetic variation. Of course one has to tread softly in this area, there are the inevitable confounds of environment, as well the unfortunate probability of any given locus being of small effect size in its influence on any given trait.

ResearchBlogging.orgA new paper in Genome Research reports a SNP which seems to have been subject to natural selection in Eurasians within the last 10,000 years. This variant is located within an exon on a gene, GIP, which produces peptides critical in the regulation of various metabolic pathways, in particular insulin response. A possible biomedical relevance to risk susceptibility is then explored subsequent to the evolutionary genomic preliminaries. Adaptive selection of an incretin gene in Eurasian populations:

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The short life expectancy of longevity genes (?)

By Razib Khan | July 8, 2010 12:39 am

When I first heard in the media there was a new study of longevity which had produced a model based on your SNP profile that was “77% accurate” as to whether you’d live to the age of 100 or not, I assumed this was confusion or distortion (perhaps The Daily Mail had broken embargo first and its spin was percolating around the mediasphere). But later I listened to one of the researchers on the radio, and though he seemed to want to tone down the certitude as to that prediction, he did not debunk the claim. Whatever the details, I did not believe that the model was that relevant to most people since very few are going to make it deep into their nineties in any case (I did have a grandfather who made it to 100 [in Bangladesh!], so my chance is presumably greater than the norm). The model would be moving you along the margins. Additionally, over the years it has paid off to be skeptical of the discovery of large effect genes for X, Y and Z. When the X, Y and Z has medical significance I’m even more skeptical, because the non-scientific biases within medical research seem to be really strong. There’s a lot of fame and money to be had. Some of the media were asking the researchers up front whether this might unlock the genetic “Fountain of Youth.” This is entrancing stuff.

So is this post from Dr. Daniel MacArthur, Serious flaws revealed in “longevity genes” study, warrants notice:

If the paper’s claims were true they would be truly remarkable. However, the general feeling from the GWAS community is that the identified associations are likely to be largely or even entirely artefactual, the result of failing to fully control for differences in the genotyping methods used in the cases and controls. The study used a mixture of two different genotyping platforms (albeit both made by Illumina) for their centenarians, while the control data was taken from an online database containing samples examined using multiple platforms. Disturbingly, similar potential genotyping bias also affects their replication cohort.

In the Newsweek piece I mentioned yesterday Kári Stefánsson has this to say about one of the platforms:

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CATEGORIZED UNDER: Medicine
MORE ABOUT: Genetics, Longevity

Don't genetically profile yourself just yet…perhaps

By Razib Khan | July 7, 2010 10:52 am

Newsweek has a long piece up which reviews some major issues with the new study of centenarians that’s been all over the media right now. Ed Yong already covered the paper, but I’m going to look at the details myself. Here’s a update from the Newsweek post:

Within an hour of this story’s publication, the Science study’s authors released a statement which a BU spokeswoman described as appearing “because of your inquiry and a similar one from the New York Times concerning methodology used to test 2 of the 150 genetic variants.” Here is what the statement says: “Since the publication of our study in Science, which was extensively peer-reviewed, a question has been raised about two elements of the findings. One has to do with two of the 150 genetic variants included in the prediction model, while the other is related to the criteria used to determine the significance of the individual variants. On the first concern, we have been made aware that there is a technical error in the lab test used on approximately 10% of the centenarian sample that involved the two of the 150 variants. Our preliminary analysis of this issue suggests that the apparent error would not effect the overall accuracy of the model. Because the issue has been raised since the publication of the paper, we are now closely re-examining the analysis. Another question that was raised concerns the criteria used to determine if an association between a genetic variant and exceptional longevity was statistically significant. We used standard criteria for the analysis, and we are confident that the appropriate threshold was used.”

CATEGORIZED UNDER: Medicine
MORE ABOUT: Genetics, Medicine

Malnutrition now, arthritis later?

By Razib Khan | July 7, 2010 2:03 am

Of Moose and Men: 50-Year Study Into Moose Arthritis Reveals Link With Early Malnutrition:

“As the study entered its second decade there was increasing evidence of Osteoarthritis (OA) in the moose population,” said lead author Rolf Peterson from Michigan Technological University. “OA is a crippling disease and is identical to that found in humans. It is commonly believed to be caused by ‘wear and tear,’ but the complex causes have remained poorly understood.”

Over the course of the study the team discovered a rise in OA as the moose population increased, and a decrease when the population fell, leading to the idea that OA is linked to moose malnutrition when food is scarcer. The team found moose that were malnourished when young would develop OA in older age.

“We have shown how malnutrition early in life increased the risk of OA later in life, but this also applies to humans as much as to a herd of moose in the wild,” said Peterson.

“These findings cast new light on how early humans first developed OA,” said co-author Dr Clark Spencer Larsen, an anthropology expert from Ohio University. “The study of human remains from archaeological contexts reveals OA increased where societies changed from foraging plants and animals to an increased dependency on farming.”

Such changes were documented in a mid-continental population of Native Americans 1000 years ago. In this group arthritis increased by 65% as society turned from foraging and hunting to agriculture and the cultivation of maize.

“Initially the increase in OA was put down to increased joint stress due to the labour of agriculture. However research now shows that, like the moose in Isle Royale, nutritional deficiencies early in life may have been the main cause. Early malnutrition was certainly a part of existence for many pre-historic human societies, and remains a fact of life for millions of people across the world, so this study is also relevant for modern human society.”

The original paper is in Ecology Letters, and it should be online at this address. I do wonder if more detailed understanding of the long term impact of early life nutrition is going to drive parents crazy with alarm as every new study which comes out produces a shift in recommendations.

CATEGORIZED UNDER: Medicine
MORE ABOUT: Aging
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