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SUNDAY SCIENCE: THESE GENES CAN HAVE THE OPPOSITE EFFECTS DEPENDING
ON WHICH PARENT THEY CAME FROM  
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Rachel Fieldhouse
August 7, 2025
Nature [[link removed]]

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_ New approach finds ‘parent-of-origin’ effects in more than a
dozen genes — without the need for parental data. _

Children inherit two copies of most genes from their parents, but one
copy of certain genes can be silenced., Oscar Wong/Getty

 

The effect of a gene can vary greatly — and sometimes be the
complete opposite — depending on whether it is inherited from the
mother or the father. Some genetic variants can, for instance,
increase a person’s risk of developing type 2 diabetes when
inherited from the father, but lower it when inherited from the
mother. But such effects have been challenging to unpick owing to gaps
in genomic data. A study published in _Nature_ this week describes
a statistical method
[[link removed]] used to identify
at least 30 parent-of-origin effects1
[[link removed]] in 14
genes.

When a child is conceived, it inherits two copies of almost every gene
— one from each parent — and both are generally turned either on
or off [[link removed]]. But in
some regions of the genome, one copy can be turned on, or expressed,
while the other is silenced. This can lead to ‘imprinting’
disorders such as Prader-Willi syndrome, which is usually caused by a
missing or non-functional paternal copy of the _UBE3A_ gene on
chromosome 15. In contrast, a missing or non-functional maternal copy
can cause Angelman syndrome.

Researchers have for decades suggested that the silencing of certain
genes is driven by an evolutionary conflict between maternal and
parental origin. For instance, the expression of paternal genes would
promote the growth of offspring during pregnancy, but that would come
at the cost of the mother’s resources. By contrast, the expression
of maternal genes would help to conserve the mother’s resources so
that she can have more children at the expense of her current
offspring’s growth. But studying how parent-of-origin variants
affect human traits is difficult because researchers usually need
genomic data from a person and their parents, which are not often
available.

Any relative

To avoid the need for parental genomic data, a research team in Europe
and the United States developed a statistical method that can infer
the parent of origin for genetic variants using genomic data that are
available from any relatives.

The team determined the parental origin of genes for nearly 109,000
people whose genomic data are included in the UK Biobank. Among those,
they identified roughly 30 variants that had differing effects on
growth and metabolism, including 19 that had a ‘bipolar’ effect,
meaning that it would have opposite effects depending on which parent
it came from. Around half of these bipolar variants were located on
chromosome 11, which hosts a large cluster of imprinted genes
associated with controlling growth. One of these variants increased
the risk of developing type 2 diabetes by 14% when inherited from the
father but decreased it by 9% when inherited from the mother.

The team repeated its analysis and confirmed its findings with data
for 85,000 people in the Estonian Biobank and 42,000 in the Norwegian
Mother, Father and Child Cohort Study. They also used the Norwegian
and UK data to show that a variant on a gene called _KLF14_ was
associated with a higher body mass index in infancy if it was
inherited from the mother.

Zoltán Kutalik, a co-author and statistical geneticist at the
University of Lausanne in Switzerland, says that the team was
surprised by the number of variants it found with opposing effects on
traits. “What was even more surprising was that all of these were
related to growth and metabolism,” he adds.

The method used is the biggest novelty of the study, says Michael
Gabbett, a geneticist at the Queensland University of Technology in
Brisbane, Australia. “The end finding that there’s a
parent-of-origin effect is not particularly novel, but the way that
they’ve gone about it really does set up a method so that we can use
these biobanks for further discovery,” he adds. Gabbett says the
method could be used to find more parent-of-origin effects.

Kutalik says that the findings need to be verified in studies with
larger, more diverse populations. The current study is also limited
because the team could not determine whether effects were caused by
which parent contributed the variant or were influenced by their
environment, such as how children were raised.

_doi: [link removed]

References

*
Hofmeister, R. J. _et
al._ _Nature_ [link removed] (2025).

Article [[link removed]] Google Scholar
[[link removed].]

_RACHEL FIELDHOUSE is a reporter for Nature News_.

_Nature_ is a weekly international journal publishing the finest
peer-reviewed research in all fields of science and technology on the
basis of its originality, importance, interdisciplinary interest,
timeliness, accessibility, elegance and surprising
conclusions. Nature also provides rapid, authoritative, insightful
and arresting news and interpretation of topical and coming trends
affecting science, scientists and the wider public.

_Nature_'s mission statement

First, to serve scientists through prompt publication of significant
advances in any branch of science, and to provide a forum for the
reporting and discussion of news and issues concerning science.
Second, to ensure that the results of science are rapidly disseminated
to the public throughout the world, in a fashion that conveys their
significance for knowledge, culture and daily life.

Nature's original mission statement
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published for the first time on 11 November 1869.

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BBC Science Focus
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