Genetic regulation of blood cells: Proximity of a gene to a genetic
change plays an important role

Date:
September 22, 2021
Source:
Universita"t Leipzig
Summary:
Researchers have gained significant new insight into the genetic
regulation of blood cells. They achieved this by analyzing
a dataset that included more than 31,000 study participants,
to date the largest dataset of its kind.



FULL STORY ========================================================================== Genetic causes of traits and diseases are being intensively researched
today.

And more than 250,000 such connections are now known. In many of these
cases, however, it is unclear how the genetic variant found affects the corresponding trait. One possible explanation is that the genetic variant affects gene expression, that is, how the gene is read, and thus alters
trait expression.


==========================================================================
The international eQTLGen Consortium has therefore conducted large-scale research on how genetic variants influence the expression of genes in
the blood. A major finding of the study was that genetic regulations
were found in close proximity to the gene in 88 per cent of all the
genes analysed. These are called cis effects. It was also shown that 37
per cent of the trait-related genetic variants studied were regulated
by distant genes, a phenomenon called trans effects.

Mechanisms identified that determine the first occurrence of menstruation
The many cis and trans effects on gene expression found offer numerous
new ways to explain molecular relationships for a wide range of traits
and diseases. For example, researchers identified trans mechanisms
caused by the gene ZNF131 that determine the first occurrence of
menstruation. In some cases, these mechanisms have already been confirmed
in the laboratory. Another such example is new mechanistic insight into
how the FADS1 and FADS2 genes influence fatty acid metabolism.

"The results significantly expand our knowledge of how gene expression
in the blood is regulated and go far beyond the information in databases currently available such as GTEx, the world's largest database to date,"
said Professor Markus Scholz. "We expect this to provide us a better understanding of genetic associations. Although not typical for the
sciences, other study groups were already using the data from our study
to interpret the genetic associations they found before it was even
published," said the Leipzig bioinformatics researcher.

Data from 7524 subjects and patients at Leipzig University's Faculty of Medicine The Consortium, established in 2014, included 37 studies with
a total number of 31,684 subjects and patients. Leipzig University's
Faculty of Medicine contributed significantly to the overall numbers as
the data analysed from its three cohorts (Sorben, LIFE Adult and LIFE
Heart) came from 7524 individuals.

The Consortium was established by researchers from the Institute of
Medical Informatics, Statistics and Epidemiology (IMISE) and led by a
team from the University of Groningen. The researchers also developed
a comprehensive analysis plan together. "The analyses are very complex
because, for one thing, several billion tests are performed and the
control of the error rate has to be tailored to the type of correlations
being studied," said Dr Holger Kirsten, a researcher at IMISE.

========================================================================== Story Source: Materials provided by Universita"t_Leipzig. Note: Content
may be edited for style and length.


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1300 DOI: 10.1038/s41588-021- 00913-z ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210922121845.htm

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