Mystery of Missing Heritability Solved?
By Dr. Mae-Wan Ho
Institute of Science in Society
EXCERPTS: Genome-wide scans for genes that determine susceptibility to common diseases have yielded little because most of those genes do not exist; disease genomics is a science fantasy that wastes time and money while the health of the nation deteriorates.
Where are all the promised genes?
When the human genome sequence was announced in 2000, President Clinton said it would “revolutionise the diagnosis, prevention and treatment of most, if not all human diseases.” Ten years on, and Fortune magazine called it: “The great DNA letdown”.
A poll by science journal Nature returned the verdict: “the hoped for revolution against human disease has not arrived.”
That is as some of us had predicted.
The human genome project has generated reams and reams of data since its inception, but there is little progress even in the apparently simple task of finding the genes responsible for susceptibility to common diseases.
Top geneticists now admit that human genetics has been haunted by the mystery of “missing heritability” of common traits.
Heritability is technically the proportion of the variability of the trait in a population due to genes. Variability is measured statistically as variance, the sum of the squared individual deviation from the population mean. Heritability is commonly referred to as the ‘genetic component’ of the variance as opposed to the proportion due to the environment, the ‘environmental component’. Note that heritability refers to the variation, and not to the trait itself.
Heritability changes according to the environment. It is not uncommon for the heritability of traits such as milk yield or height of a plant from the same genetic strain to change substantially from one year to the next. However, there is a tendency for some scientists as well as the popular media to mistakenly assume that any trait with a large heritability means it is predominantly genetically determined, which is definitely not the case.
Eric Lander and his team at Board Institute MIT & Harvard are among those suggesting that much of the missing heritability never existed in the first place. They base their argument on biometrical genetics, a mathematical discipline that deals with continuously varying traits, such as crop yields, height, body mass, IQ scores, or disease states that fall on a continuum, as for example, blood glucose, blood pressure, or some measure of disease severity.
One arrives at precisely the same conclusion given the pervasive epigenetic influences of the environment on development, which have been abundantly confirmed and extended since the human genome was sequenced.
We now know that much of the variation may come from individual experiences of the environment; furthermore, those experiences can mark and change genes, influencing the development of the individual and in many case, the individual’s offspring.
Genes and the environment operate in enormously complex feed-forward and feed-back networks that straddle generations. This fundamentally circular causation between genes and environment means that genetic and environmental contributions are inseparable, and any attempt at assigning linear effects to single genes is doomed to failure.
Read the full and fascinating report at Institute of Science in Society