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Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4
Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,43...
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Published in: | Nature communications 2021-11, Vol.12 (1), p.6618-6618, Article 6618 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
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Online Access: | Get full text |
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Summary: | Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in
DUSP1
,
NOTCH4
, and
SLC9A4
to be associated with eczema. In
DUSP1
and
NOTCH4
missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at
SATB1-AS1
/
KCNH8
,
TRIB1
/
LINC00861
,
ZBTB1
,
TBX21
/
OSBPL7
, and
CSF2RB
are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.
Genetic studies of eczema to date have mostly explored common genetic variation. Here, the authors perform a large meta-analysis for common and rare variants and discover 8 loci associated with eczema. Over 20% of the heritability of the condition is attributable to rare variants. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-021-26783-x |