RT Journal Article
T1 Exploring Impact of Rare Variation in Systemic Lupus Erythematosus by a Genome Wide Imputation Approach.
A1 Martínez-Bueno, Manuel
A1 Alarcón-Riquelme, Marta E
K1 GWAS—genome-wide association study
K1 SLE
K1 aggregated case-control enrichment
K1 imputated rare variation
K1 sequence kernel association test
K1 systemic lupus erythematosus
AB The importance of low frequency and rare variation in complex disease genetics is difficult to estimate in patient populations. Genome-wide association studies are therefore, underpowered to detect rare variation. We have used a combined approach of genome-wide-based imputation with a highly stringent sequence kernel association (SKAT) test and a case-control burden test. We identified 98 candidate genes containing rare variation that in aggregate show association with SLE many of which have recognized immunological function, but also function and expression related to relevant tissues such as the joints, skin, blood or central nervous system. In addition we also find that there is a significant enrichment of genes annotated for disease-causing mutations in the OMIM database, suggesting that in complex diseases such as SLE, such mutations may be involved in subtle or combined phenotypes or could accelerate specific organ abnormalities found in the disease. We here provide an important resource of candidate genes for SLE.
YR 2019
FD 2019-02-26
LK http://hdl.handle.net/10668/13696
UL http://hdl.handle.net/10668/13696
LA en
DS RISalud
RD Apr 7, 2025