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Grossvater
12-26-2013, 04:37 AM
I just saw this link on another forum. According to this article, the tendency for diabetes in Native Americans is an inherited trait from Neanderthals. Do you think there is anything to it or is this a bunch of poppycock? I work with Native Americans and the prevalence of diabetes among the Indians on my reservation is overwhelming.

http://www.examiner.com/article/genetic-risk-factor-for-type-2-diabetes-went-from-neanderthals-to-modern-peoples

DMXX
12-26-2013, 07:24 AM
Given this was a genome-wide association study (GWAS), this gene was objectively determined to be a contributing factor to the phenotype in question (diabetes mellitus, DM). These programs are excellent at locating candidate genes. As part of my medical training I've been dabbling in GWAS lately and the inferences are quite something. Even with the standard caveats (e.g. population size) There's little doubt this mutation has a major role in DM predisposition among this group.

We've now established that there's some Neanderthal admixture (between 4-7% if I remember the original study from 2012) in human groups outside of Africa. This would logically include Native Americans. We also don't have any reason to presume the components of this Neanderthal admixture was uniformly distributed among non-African humans. Thus, it's quite possible that one non-African group inherited a certain trait from Neanderthals which is rarely seen among others.

The only room to manoeuvre comes with definitively stating this mutation comes from Neanderthals. How do we know this is the case? Do we have enough Neanderthal samples with this mutation from a wide geographical zone to make the case for this? Can we rule out non-African human admixture in Neanderthals as a contributing source, making the mutation a H. Sapiens Sapiens one after all? I haven't been following the archaic Hominid developments this year closely, so I'm trusting the better-informed amongst us to address these questions... If they can be addressed at this stage, that is!

That being said, it's highly improbable DM in itself is derived from Neanderthals considering it occurs in practically every human group (not just non-Africans) and the commonest cause in Westerners is environmental rather than genetic susceptibility.

Joe B
12-26-2013, 06:26 PM
I just saw this link on another forum. According to this article, the tendency for diabetes in Native Americans is an inherited trait from Neanderthals. Do you think there is anything to it or is this a bunch of poppycock? I work with Native Americans and the prevalence of diabetes among the Indians on my reservation is overwhelming.

http://www.examiner.com/article/genetic-risk-factor-for-type-2-diabetes-went-from-neanderthals-to-modern-peoples
DMXX is spot on. He has access to peer-reviewed journals such as Endocrinology (http://press.endocrine.org/journal/endo).

The American Diabetes Association has some good stuff with the Awakening the Spirit (http://www.diabetes.org/in-my-community/programs/native-american-programs/awakening-the-spirit.html) program.

Years ago, Native Americans did not have diabetes. Elders can recall times when people hunted and gathered food for simple meals. People walked a lot. Now, in some Native communities, one in two adults has diabetes.
American Diabetes Association

Awakening the Spirit (http://www.diabetes.org/in-my-community/programs/native-american-programs/awakening-the-spirit.html)
American Indian/Alaska Native Programs (http://www.diabetes.org/in-my-community/programs/native-american-programs/)

Indian Health Service has the Division of Diabetes Treatment and Prevention (http://www.ihs.gov/MedicalPrograms/Diabetes/) and a lot of information too.

Good Luck.

AJL
12-26-2013, 07:53 PM
This classic paper (http://www.diabetes.ca/files/OjiCreeHegeleSept03.pdf) is also of interest.

Wonder_Wall
12-26-2013, 07:59 PM
I read an article on this yesterday.

Apparently this gene variant accounts for some of the diabetes in populations who carry it. But it is only one of many diabetes "genes". This can give a person with Mexican or Native American ancestry a 40% increase in lifetime risk for type II diabetes.

That's significant. It apparently accounts for a quarter of the difference in diabetes rates between Europeans and folks with significant Native American ancestry.

Joe B
12-26-2013, 09:48 PM
The Canadians have been doing a lot of work in this area. Looks like Australia has similar health issues too.
Diabetes hits earlier in First Nations, kidney team finds (http://www.cbc.ca/news/health/diabetes-hits-earlier-in-first-nations-kidney-team-finds-1.2448134) CBC Posted: Dec 02, 2013

Canadian Medical Association Journal Press Release
First Nations adults have more than double the risk of end-stage kidney disease CMAJ December 2, 2013
http://www.cmaj.ca/site/misc/pr/2dec13_pr.xhtml

"Because they are younger than non–First Nations individuals when diabetes first develops, First Nations individuals are more likely to survive long enough for end-stage renal disease to occur, presumably because of lower cardiovascular mortality," writes Dr. Roland Dyck, a professor with the departments of Community Health and Epidemiology, and Medicine, University of Saskatchewan, with coauthors.
In a journal editorial accompanying the study, Dr. Stephen McDonald of the renal unit at Royal Adelaide Hospital in Australia noted excess rates of diabetes have also been documented among indigenous groups in the U.S., Australia and New Zealand.
"Despite as higher prevalence of heavy albuminuria among First Nations people, we did not find that the presence or severity of albuminuria conferred an additional risk to the development of kidney failure," writes Dr. Brenda Hemmelgarn, Department of Community Health Sciences, University of Calgary, with coauthors. "Even among participants with no measure of albuminuria, risk of progression to kidney failure was similarly elevated for First Nations compared with non–First Nations participants within each category of estimated GFR [glomerular filtration rate]." Usually there is a strong association between proteinuria and kidney disease so that is surprising.

Differential mortality and the excess burden of end-stage renal disease among First Nations people with diabetes mellitus: a competing-risks analysis CMAJ December 2, 2013
http://www.cmaj.ca/content/early/2013/12/02/cmaj.130721

Placing Aboriginal kidney disease in context CMAJ December 2, 2013
http://www.cmaj.ca/content/early/2013/12/02/cmaj.131605.extract

Association between First Nations ethnicity and progression to kidney failure by presence and severity of albuminuria CMAJ December 2, 2013
http://www.cmaj.ca/content/early/2013/12/02/cmaj.130776

AJL
12-26-2013, 10:39 PM
It actually makes a fair bit of sense that a primarily hunter-gatherer society would develop genetics to absorb more caloric value from their food, as compared to a farmer society. There being several genomic associations with elevated diabetes risk in mainly hunter-gatherer-descended populations is another way of saying that different mutations arose independently that helped various peoples stave off the worst effects of a lifestlye where the food source was less than stable.

Little bit
12-27-2013, 01:20 PM
Apparently this gene variant accounts for some of the diabetes in populations who carry it. But it is only one of many diabetes "genes".

I get an uncommon version for rs4994, GG, which 23andme has in the "Response to exercise" report curiously described as:
"Decreasing calorie intake and increasing physical activity through walking is not associated with weight loss."

Of my 100 or so extended sharers, I am the only GG, 19 are AG and 5 of those are my relatives. Linking out to OMIM, the variant is linked with obesity and diabetes risk, especially gestational diabetes, which I did develop in both pregnancies despite being thin. I wondered why such a variant would exist but I've also seen it linked to exceptional endurance so I'm guessing it's some kind of "thrifty" gene. On Opensnp, only a handful of us are GG for the snp, including Denisova hominin:
http://opensnp.org/snps/rs4994#users

Táltos
12-28-2013, 03:56 PM
I get an uncommon version for rs4994, GG, which 23andme has in the "Response to exercise" report curiously described as:
"Decreasing calorie intake and increasing physical activity through walking is not associated with weight loss."

Of my 100 or so extended sharers, I am the only GG, 19 are AG and 5 of those are my relatives. Linking out to OMIM, the variant is linked with obesity and diabetes risk, especially gestational diabetes, which I did develop in both pregnancies despite being thin. I wondered why such a variant would exist but I've also seen it linked to exceptional endurance so I'm guessing it's some kind of "thrifty" gene. On Opensnp, only a handful of us are GG for the snp, including Denisova hominin:
http://opensnp.org/snps/rs4994#users
Interesting Little bit I just looked this up for my Mom's 23andme. Her rs4994=AA, mine from FTDNA=AA as well. 23andme also shows some other ones that I can't find in my FTDNA data of course. For my Mom rs1800588=CC which means Exercise is associated with a 5% improvement in insulin sensitivity, on average according to 23andme. And rs1801282=CG which according to 23andme means Glucose tolerance improved with regular exercise. These two markers they have marked as being applicable to European ethnicity. The one you provided they have marked as being applicable to Asian.

I too had gestational diabetes while pregnant despite being thin. The most weight I had gained was 35 lbs during pregnancy. So at 5'7" my top weight ever was 170 lbs. It was pretty funny as you couldn't tell I was pregnant until I turned around! Anyway I have read that developing gestational diabetes has implications for you possibly going on to developing type 2 diabetes, and maybe for your child. In my family I am the only person that is known to have developed gestational diabetes. My paternal grandfather though was diabetic and had to take insulin. The only thing that I can know for sure from any DNA tests about him (from my brother) is that his y DNA was Q1b1a.

To tie back into the original post, I have seen several articles online that had been linking the higher incidence of diabetes in Native Americans to their mtDNA.

authun
01-02-2014, 11:56 AM
According to this article, the tendency for diabetes in Native Americans is an inherited trait from Neanderthals. Do you think there is anything to it or is this a bunch of poppycock?

I think it is a false assocation. A predisposition to diabetes has some genetic foundation because of the way we metabolise alpha carbohydrates. The way in which we do it varies within populations and tipping points vary hugely between individuals. It is ancient though and is mentioned in the earliest scripts. It wasn't frequent though. We don't metabolise beta carbohydrates anymore with the single exception of the beta disaccharide lactose, for which some humans do produce an enzyme, lactase. But, even then different lactase persistent groups have different genes responsible for its production.

Modern diets which include highly refined carbohydrates, especially sugars in convenience, fast or comfort foods increase the prevalence of diabetes. One only has to look at the population of Nauru, one of the healthiest populations in the 1960s/70s, who now have a diabetes frequency of over 30%. They became modern and wealthy because of mining, changed their diet, ate the wrong foods and ended up being the world's number one.

Isolating the genetic causes however is difficult as the exact etiology of type 2 diabetes is not understood. We have a reasonably good idea and we sort of know some of the genes involved. But, we don't know why some individuals have a greater tendency to lay down fats in the liver and pancreas than others or why some are able to cope with larger amounts than others. Not knowing the genes resposnsible makes it impossible to date them to the neolithic.

"Explanations for the epidemic proportions of diabetes, heart disease, obesity and hypertension in Nauru include: urbanization, low physical activity, the importation of processed foods and a diabetic genotype. After independence in 1968, Nauru became the smallest and richest republic (per capita) in the world by exploiting large deposits of phosphate. During a period of excessive wealth, the indigenous population in Nauru, which is predominantly of Micronesian ancestry, became more dependent on store-bought food and accustomed to a sedentary lifestyle."

Prevalence and risk factors of diabetes and impaired fasting glucose in Nauru (http://www.biomedcentral.com/1471-2458/11/719)

The real change is the food and how you metabolise it is genetic, but it is only part of the story so to pinpoint it to the Neanderthals smacks more of attention seeking headlines than science.

Mehrdad
03-30-2014, 03:59 PM
Diabetes is also very prevalent among polynesians, perhaps diet is the largest factor amongst Pacific islanders

Jasper85
10-22-2014, 09:48 AM
The higher-risk version of this gene is seen in up to half of people who have recent Native American ancestry, including Latin Americans. The fact that this gene mutation is more common in Latin Americans could account for as much as 20 percent of their increased levels of Type 2 diabetes. The researchers noted changing levels of the protein that the gene encodes could alter the amount of a specific type of fat, one that prior studies have linked to the risk of diabetes.

DMXX
02-10-2015, 12:03 PM
Just a point of interest in case anyone is still interested in this paper's findings; it wasn't a single point mutation on a given SNP which was found to be associated with type 2 diabetes among Native American populations. Rather, a haplotype (i.e. string of conserved alleles) was.

I've recently spent hours looking at the raw SNPs from dozens of studies and the conclusions of various papers involved in complex traits. There is absolutely no way type 2 diabetes is even partially derived from Neanderthals in Homo Sapiens Sapiens; there are just too many risk variants across too many genes across too many chromosomes across too many populations for that to even be possible. Furthermore, many of these risk variants are common across all world super-populations, so no individual in their right mind after enough familiarisation with African, European, East Asian etc. GWAS can even claim it might be due to an OoA admixture event with Neanderthals.

In sum, this paper basically identified a novel and specific predisposing genetic factor for type 2 diabetes among Native American derived populations. Even then, it isn't the only predisposing factor. Other risk variants shared with Eurasians and Africans are also observed.

It isn't often I speak (type? :) ) in such absolute terms, so the weight of that should be appreciated. Here's an important paper along those lines in case anyone's interested in having a time-efficient but firm grasp on this (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003566). It's an awesome paper with plenty of information on complex disease (extends well beyond diabetes). A touch out of date, but still very much relevant.

rock hunter
03-04-2015, 11:58 PM
I don't know, unless neanderthals had Twinkies and Klondike bars I do not believe diabetes was an issue. I think when we started to refine sugars and eat massive amounts of it, it caused problems we were never designed for or needed to mutate something to protect us from.