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Common-Variant Common-Disease Hypothesis Contributed by Michael Joyner
One widely assumed outcome of the Human Genome Project (HGP)
was that a limited number of gene variants based on
so-called single nucleotide polymorphisms (SNPs) would
explain much of the risk of common non-communicable diseases
like ischemic heart diseases, type II diabetes, hypertension
and other conditions including some forms of cancer.
This is known as
Common-Variant
Common-Disease Hypothesis and was underpinned by the
well-known observation that many diseases run in families
and are heritable in a statistical sense.
However, these conditions do not have classic
Mendelian patterns of heritability, as for example, certain
forms of hemophilia, sickle cell anemia, or cystic fibrosis
do. In this
context, the results of numerous Genome Wide Association
Studies (GWAS) conducted in large populations of humans have
found:
·
A large number of gene variants (sometimes hundreds) are
associated with many common diseases.
·
The effect size of such variants is typically small.
·
The reproducibility GWAS studies from one study or
population to the next can be problematic.
·
The distribution of variants in populations with and without
a given disease is frequently similar.
·
The addition of gene scores to disease risk prediction
algorithms derived from epidemiology studies has generally
not improved the algorithms.
These findings highlight the ongoing problem of “missing
heritability” which has been a concern since studies from
the Victorian era on the relationship between the height of
parents and their children.
For those who favor a DNA centric view of human
phenotypic variability the assumption is that more detailed
studies of the genome will shed light on DNA based
mechanisms that might account for this missing heritability.
Those who favor the view that human phenotypic
variability is due to complex interactions between the
environment, behavior, physiological regulation and
adaptation, and the genome see the continuing challenge of
missing heritability as highlighting the limitations of the
DNA centric view of human phenotypic variation.
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| The MUSIC of Life: Biology Beyond the Genome ©Denis Noble |
