January 19, 2010
New Diabetes Genetic Variants Found
More genetic variants that influence blood sugar and insulin have been identified.
A major international study with leadership from Massachusetts General Hospital (MGH) researchers has identified 10 new gene variants associated with blood sugar or insulin levels. Two of these novel variants and three that earlier studies associated with glucose levels were also found to increase the risk of type 2 diabetes. Along with a related study from members of the same research consortium, associating additional genetic variants with the metabolic response to a sugary meal, the report will appear in Nature Genetics and has been released online.
"Only four gene variants had previously been associated with glucose metabolism, and just one of them was known to affect type 2 diabetes. With more genes identified, we can see patterns emerge," says Jose Florez, MD, PhD, of the MGH Diabetes Unit and the Center for Human Genetic Research, co-lead author of the report. "Finding these new pathways can help us better undertand how glucose is regulated, distinguish between normal and pathological glucose variations and develop potential new therapies for type 2 diabetes.
This study illustrates how declining costs of genetic testing cause much larger steps forward in discovery of significant genetic variants. The 4 previously discovered genetic variants were probably not all discovered in the same scientific paper. Then along comes one piece of research that reports two and a half times more genetic variants in blood sugar and insulin levels than were previously known. The rate of discovery goes up because the scale of genetic testing has risen so much due to big drops in costs.
122,000 people and 2.5 million locations (SNPs or single nucleotide polymorphisms) in human genomes were examined.
Both studies were conducted by the Meta-Analyses of Glucose and Insulin-related Traits Consortium (MAGIC), a collaboration among researchers from centers in the U.S., Canada, Europe and Australia that analyzed gene samples from 54 previous studies involving more than 122,000 individuals of European descent. The study co-led by MGH scientists – along with colleagues from Boston University, University of Cambridge, University of Oxford and the University of Michigan – began by analyzing about 2.5 million gene variations (called SNPs) from 21 genome-wide searches for variants associated with glucose and insulin regulation in more than 46,000 nondiabetic participants. The 25 most promising SNPs from the first phase were then tested in more than 76,000 nondiabetic participants in 33 other studies, leading to new associations of nine SNPs with fasting glucose levels and one with fasting insulin and with a measure of insulin resistance.
More genetic variants for glucose and insulin levels await to be found.
"We were delighted that we were able to find so many SNPs associated with raised levels of glucose," says Dr Inęs Barroso, from the Wellcome Trust Sanger Institute, "but amazed that we found only one strong association with levels of insulin. We don't think this is a technical difference, but that the genetics is telling us that the two measures, insulin and glucose, have different architectures, with fewer genes, rarer variants or greater environmental influence affecting insulin resistance."
The team have strong evidence that other genetic factors remain to be found: their study explains about ten per cent of the genetic effect on fasting glucose. They believe that there will be rarer variants with a larger impact that would not be found by a study such as this.
In the next 5 years we'll witness more discoveries about the meaning of genetic variants than we've seen in all previous history because genetic testing costs have fallen so far so fast. Costs have dropped by orders of magnitude and continue to drop rapidly. Scientists face a flood of data from which they will be able to tease out many discoveries.
"In the next 5 years we'll witness more discoveries about the meaning of genetic variants than we've seen in all previous history because genetic testing costs have fallen so far so fast. Costs have dropped by orders of magnitude and continue to drop rapidly. Scientists face a flood of data from which they will be able to tease out many discoveries."
If I could, I would take the opposite side of that bet on even money... I want to bet against the proposition that the genetic etiology (most of it) of the race differences in intelligence will be found in five years (or even between race variances)...
I would win in at least three ways:
1) Biotech advance rates would be much lower than you anticipate
2) The genes will not be found even if more analysis has been done
3) political forces inhibit research
So far, GWAS (genome wide association studies) haven't found many polymorphisms that explain IQ differences within each race although they primarily searched for IQ differences in the protein-coding part of the genome. Furthermore, there seems to be two much noise that makes it hard to find single genes that lead to genetic differences such as gene-environment interactions, epistasis, and perhaps that genetics doesn't play a very significant role in determining the phenotype of IQ (it does play an important role, but most HBDists cite the .8 broad sense heritability based on twin studies [showing that this group isn't that objective and are primarily concerned with confirming their preconceived views on the inferiority of certain races] when it could be a more moderate .6 .) Genes that do affect IQ only have a minute effect thus they would be very hard to locate and require a lot of statistical power. Whole genome sequencing will find more variants related to IQ, but this approach would inevitably lead to more false positives (since more variables are being tested)
" September 08, 2005
I've been expecting the left-liberal inequality taboo to die by 2015. But declines in the cost of DNA sequencing combined with research results such as that reported above make me more optimistic. The taboo might have only about 5 more years to run."
It is far from being dead now... and I am quite confident that it would not die within the next five years.
The trade publication Genomeweb has an excellent article up today, Study Suggests Non-Genetic Factors are Better Type 2 Diabetes Risk Predictors than Genetics (free subscription required). It includes a synopsis of a recent British Medical Journal article.
As part of the larger Whitehall II prospective cohort study, researchers from the University College London followed thousands of individuals in London's Whitehall district over roughly 20 years. When they looked specifically at factors affecting type 2 diabetes risk, they found that two non-genetic risk models were better predictors of diabetes risk than a genetic model based on nearly two dozen risk alleles.
When the researchers assessed the so-called Cambridge and Framingham type 2 diabetes risk models, which are based on non-genetic factors such as age, sex, family history, waist circumference, body mass index, smoking behavior, cholesterol levels and so on, they found that both predicted risk of the disease better than a genetic risk model based on 20 common, independently inherited risk SNPs.
The Cambridge model had 19.7% sensitivity for detecting type 2 diabetes cases in the Whitehall cohort based on a 5% false positive rate, while the Framingham model had 30.6% sensitivity. The gene count score, meanwhile, detected 6.5% of cases at a 5% false positive rate and 9.9% of cases at a 10% false positive rate.
In addition, the team noted, adding genetic risk information did not significantly improve the ability to identify individuals at risk of type 2 diabetes over either non-genetic risk model alone...
Of course, the key here is how the 20 SNPs discussed in this BMJ
article compare to the newly-identified SNPs characterized by the MAGIC collaboration. Are some of them the same? I haven't checked.
From the original article:
"The team have strong evidence that other genetic factors remain to be found: their study explains about ten per cent of the genetic effect on fasting glucose. They believe that there will be rarer variants with a larger impact that would not be found by a study such as this. "
"122,000 people and 2.5 million locations (SNPs or single nucleotide polymorphisms) in human genomes were examined."
Hmm... Robert Plomin recently (2008) conducted a study using 500k SNPs with 7000 7 year old children and only 6 SNPs (each very small effect with each one causing less than 0.4% of IQ variance). It seems that Plomin's study is rather underpowered. I also wonder if the results from both of these studies can be replicated.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408663/pdf/gbb0007-0435.pdf (The Plomin PDF)
Just testing if your new policy censors me specifically or with links...
Most of the children are twin pairs...
Apparently, an out-of-date blacklist caused a bunch of people's posts to get moderated. It seems fixed now, though.