4 | Test candidate SNPs in lots of samples
snp candidates surviving the first two rounds are then tested in many
other groups of people, comparing cases and controls to come up
with a final short list of candidate snps.
k snps tested 5–50
k statistical hurdle: low
5 | Which genes are involved?
after identifying the snps linked most strongly to the disease, the
next step is to identify which genes are involved, using the previously
identified snps as a guide. those snps will probably lie within or near
the important genes.
martin barraud; From duerr et al. science 314:1461(2006), reprinted with permission From aaas;
istockphoto (arekmalang, raycat, Joezellner); aFFymetriX
6 | What do the genes do?
using other tools, such as computer simulations, animal studies and
cell cultures, scientists try to figure out what the identified genes do
in the body, how the genes’ activity relates to the disease and what
steps might be taken to combat the disease.
because basically no one study is remotely
definitive,” says epidemiologist David
Hunter of the Harvard School of Public
Health in Boston. “We have to put together
consortia and large-scale collaborations.”
Still, data-sharing is becoming easier.
For example, researchers who conduct
genome-wide association studies funded
through the National Institutes of Health
must now deposit their data into a common database for immediate access.
Surprisingly, the earlier that researchers collaborate, the better — at least from
a statistical point of view, Hunter says.
Researchers originally thought that if
small, independent groups each did their
own study and then compiled a running
list of all the important SNPs from their
results, everything would be fine.
Not so, Hunter says. It turns out that
the running list of results will still miss
important SNPs. It’s better for those
groups to pool all their subjects at the
beginning and run one big scan, he says.
The final list from the pooled study will
be more accurate and complete than the
running list from independent studies.
The reason, Hunter says, is that subtle genetic effects (such as those likely
to contribute to diseases) can be picked
up only with a sufficiently large sample
size — in the same way that a larger magnifying glass is needed to spot the smaller
bugs in the undergrowth. “So this will be a
long-running story for common diseases,”
he says, “because as we put together more
and more scans, we’ll find more and more
truly associated variants.”
Also afflicting these multistage studies