52 THE SCIENTIST | the-scientist.com
PROFILEthere is a genetic component to the most common late-onset form of
Parkinson’s disease.
DeCODE also explored how the human genome has evolved.
In 2004, the team analyzed how reproductive success is affected
by the way that the maternal and paternal genomes are scrambled
during the formation of egg and sperm. They used genome-wide
microsatellite data on 23,066 individuals and came to the con-
clusion that a small portion of the genome, just 10 percent, has a
higher rate of recombination, suggesting that characteristics driven
by genes in these regions evolved faster than phenotypes coded by
genes in other parts of the genome.
It’s still not clear what these characteristics are, according to
Stefánsson, but the team is investigating this further. And while
new mutations across the genome are more likely to come from the
father (because spermatogenesis is a continuous process through-
out a man’s life while oocytes do not divide postnatally), in this 10
percent of the genetic code both the father and mother equally
contribute to the de novo mutation rate. The analysis also showed
that a high recombination rate was linked to increased viability of a
fetus, particularly in older mothers. In addition, mothers who had a
high oocyte recombination rate were more likely to have more chil-
dren. Again, the results raised more questions than they answered,
so Stefánsson and his colleagues are continuing to dig deeper.
As Stefánsson had envisioned on that fateful day in Starbucks,
human disease risk is another focus of the company. In 2009, the
deCODE team identified common genetic variants that result in
an increased risk of developing schizophrenia. “We showed that
those who carry the variant but don’t develop schizophrenia have
a departure from the norm in terms of cognition, in a similar way
as schizophrenics but not as severe,” says Stefánsson. “This sug-
gests that what comes first is the abnormality in thought and then
the schizophrenia, and not that the schizophrenia is a prerequisite
for thinking differently.”
For Stefánsson, this is among the first clues to figuring out how
thoughts develop in the brain. Another clue is that there’s an over-
representation of individuals with bipolar disorder and of healthy
siblings of people with schizophrenia and bipolar disorder among
creative professions, but, according to Stefánsson, it hasn’t been clear
whether creativity and these mental illnesses had shared biology.
“We showed that Icelandic writers, painters, and others in creative
professions have a higher predisposition for schizophrenia, suggest-
ing that at least in part, creativity and schizophrenia share biology.”
In another study, deCODE researchers uncovered a genetic link
underlying the phenomenon that individuals who obtain a higher
education typically have fewer children, showing that genetic pre-
disposition to obtain education may also predispose an individual to
have fewer children. Analyzing about 130,000 people in Iceland, the
team identified genes associated with completing higher education
(educational attainment) and found that these genes decreased in
frequency in the population between 1910 and 1990. In other words,
the genes associated with educational attainment were under nega-
tive genetic selection. If an individual harbored these “education”
genetic variants, they were also more likely to have later and fewerchildren. It was not simply a matter of investing more time in edu-
cation and thus less in childrearing: those who had these gene vari-
ants but did not attain higher education also had fewer children than
individuals who did not harbor the “education genes,” suggesting a
link between these education-associated variants and fertility.A GENOMIC FRONTIER
In 2015, Amgen bought deCODE, but Stefánsson says the biotech-
nology company has left him and his team alone to continue to make
new discoveries and publish their basic human genetics research.
DeCODE now has genealogy data on all Icelanders, blood samples
from about 160,000 of those individuals, and whole genomes on
about 60,000 volunteers who have given deCODE informed con-
sent to use their data for research. “We have sequence information
on most of the nation, which puts us in a position to do fairly pow-
erful genetics but also places a high responsibility on our shoulders
on privacy and data protection,” Stefánsson says.Iceland’s governmental bioethics committee oversees the data.
The deCODE database includes individuals’ disease-causing genes,
such as a mutation in BRCA2 that’s common among Icelanders
and confers an 86 percent probability of developing cancer on the
women who carry it, as well as increasing the risk of prostate cancer
in men. The Icelandic government, however, does not allow itself or
any private institution to provide people with their genetic informa-
tion without explicit consent. “It’s a complicated issue,” says Stefáns-
son. “It seems self-evident that anyone should have access to their
data.” But, because deCODE is sequencing data for bulk population
studies, and not in a clinical-grade laboratory, the company cannot
guarantee that each individual’s sequence is completely accurate.
Therefore, because the national law prohibits both deCODE and the
healthcare system from contacting those with disease-related genes,
the company’s solution is a website where the team has deposited
better-quality sequencing information on BRCA2 and other genes,
allowing individuals to find their data if they wish.
After 23 years at deCODE, Stefánsson says he has achieved
more than what he expected when he hatched his plan for the com-
pany in Starbucks, and he has no plans of slowing down now. “I
am extraordinarily pleased with the contributions we’ve made to
human genetics and evolution.”
While staying engaged with his research, Stefánsson still manages
to read about 40 novels a year. “Language is the equipment with which
you think, and the best way to train yourself on the use of language
is to read good literature,” he says. “Reading is as important for me as
eating. I cannot survive without it.”gI think it requires an extraordinarily dull
mind not to be fascinated by the brain.