A Big Picture, Unveiled — Genetic Architecture

Science Daily summarizes the news:

Scientists at Johns Hopkins Bloomberg School of Public Health have developed a powerful method for characterizing the broad patterns of genetic contributions to traits and diseases. The new method provides a “big picture” of genetic influences that should be particularly helpful in designing future genetic studies and understanding potential for genetic risk prediction.

Through innovative statistical techniques, researchers are now able to estimate, within certain parameters, the numbers variations in DNA that affect physical traits including, among other things, height, body mass index or BMI, body measurements, diabetes, cognitive performance, and childhood obesity.

The original paper, “Estimation of complex effect-size distributions using summary-level statistics from genome-wide association studies across 32 complex traits,” was published by Nature Genetics. Scientists are trying to figure out how many people need to be involved in a study of this type, before any meaning can be assigned to the data. Or, as it is phrased by senior author Nilanjan Chatterjee, Ph.D.,

In terms of practical results, we can now use this method to estimate, for any trait or disease, the number of individuals we need to sample in future studies to identify the majority of the important genetic contributions.

All this work is based on GWAS, an awkward acronym for genome-wide association studies, and the variations that occur within them. Variations in what? In the DNA “letters” known as single nucleotide polymorphisms, or SNPs. Of course, this branch of science is in its infancy, but the expectation is that because of it, we will understand how diseases get their foothold within the body, and how they gain permission and ability to progress.

Genetic Engineering & Biotechnology News says,

Their findings, derived from analyses of existing genome-wide association studies (GWAS), suggest that any one trait or disease risk may be associated with up to tens of thousands of single nucleotide polymorphisms (SNPs) — many more than was previously thought — each of which has a minute individual effect, but which cumulatively impact significantly on trait variability or disease risk.

Genome-wide association studies

Previous GWAS have been informative, of course, but they have generally been unable to “reveal the overall genetic architectures of diseases or traits.” Now it appears possible, because researchers have glimpsed a realm of synergy that operates with unimaginable complexity.

Importantly, this new research shows a chasm of difference between two general kinds of traits, which appear to have distinct types of genetic architecture. If matters progress to where we use genetic risk-prediction models to make important decisions, a very large caveat will have to be carved out before drastic action is taken.

When it comes to mental health and cognitive ability, the cumulative numbers used by studies, if they are to be at all useful, will have to grow by orders of magnitude. The Science Daily writer sums up the thoughts of Dr. Chatterjee:

For psychiatric diseases and cognitive traits, with their “long-tail” distributions of gene effects, diminishing returns usually won’t kick in until sample sizes are even larger, i.e., in the millions… Some complex diseases are too rare to lend themselves to sample sizes anywhere near the required number in the foreseeable future, he notes. Their genetic underpinnings may therefore remain murky, with a large-scale national and international consortium effort needed to build larger GWAS.

We will talk more about this, but something else is going on here, too, that opens up a whole bunch of new doors, or at least points to their existence. According to GenEngNews.com,

The results from GWAS also suggest that common genetic variants may have a greater impact on heritability than can be explained by SNPs.

That sentence says a mouthful! It suggests that, however monumental this recent discovery may be, it is still just a part of the story, and only a taste of what the near future has in store for humanity.

Your responses and feedback are welcome!

Source: “Broad ‘genetic architectures’ of traits and diseases,” ScienceDaily.com, 08/13/18
Source: “Study Finds Genetic Basis of Common Diseases May Span Tens of Thousands of SNPs,” GenEngNews.com, 08/14/18
Photo credit: Dun.can on Visualhunt/CC BY

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Dr. Pretlow’s invited presentation at the American Society of Animal Science 2020 Conference
What’s Causing Obesity in Companion Animals and What Can We Do About It

Dr. Pretlow’s invited presentation at the World Obesity Federation 2019 Conference:
Food/Eating Addiction and the Displacement Mechanism

Dr. Pretlow’s Multi-Center Clinical Trial Kick-off Speech 2018:
Obesity: Tackling the Root Cause

Dr. Pretlow’s 2017 Workshop on
Treatment of Obesity Using the Addiction Model

Dr. Pretlow’s invited presentation for
TEC and UNC 2016

Dr. Pretlow’s invited presentation at the 2015 Obesity Summit in London, UK.

Dr. Pretlow’s invited keynote at the 2014 European Childhood Obesity Group Congress in Salzburg, Austria.

Dr. Pretlow’s presentation at the 2013 European Congress on Obesity in Liverpool, UK.

Dr. Pretlow’s presentation at the 2011 International Conference on Childhood Obesity in Lisbon, Portugal.

Dr. Pretlow’s presentation at the 2010 Uniting Against Childhood Obesity Conference in Houston, TX.

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