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Nonconserved Long Intergenic Noncoding RNAs Associate With Complex Cardiometabolic Disease Traits.
Andrea S Foulkes1,2,3, Caitlin Selvaggi1, Tingyi Cao1,3
1Biostatistics Center, Massachusetts General Hospital, Boston (A.S.F., C.S., T.C.).
Arteriosclerosis, Thrombosis, and Vascular Biology
|November 12, 2020
Summary
Nonconserved long intergenic noncoding RNAs (lincRNAs) associate with complex cardiometabolic traits similarly to conserved lincRNAs. This suggests a need to reconsider prioritizing genetic discoveries based solely on sequence conservation.
Area of Science:
- Genomics
- Noncoding RNA Biology
- Cardiometabolic Disease Research
Background:
- Thousands of long intergenic noncoding RNAs (lincRNAs) are identified in human tissues.
- Genetic variation in lincRNAs is linked to complex cardiometabolic traits.
- The role of conserved versus nonconserved lincRNAs in disease association is unclear.
Purpose of the Study:
- To investigate whether nonconserved lincRNAs associate with complex cardiometabolic traits differently than conserved lincRNAs.
- To evaluate the pattern of association for nonconserved lincRNAs compared to conserved lincRNAs.
Main Methods:
- Utilized over 7000 lincRNA annotations from GENCODE Release 33-GRCh38.p13.
- Leveraged genome-wide association study (GWAS) summary data from large consortia (GIANT, UK Biobank, GLGC, Cardiogram, DIAGRAM/DIAMANTE).
- Analyzed associations between lincRNAs and 8 complex cardiometabolic traits.
Main Results:
- Nonconserved lincRNAs associate with cardiometabolic traits at a rate comparable to conserved lincRNAs.
- These associations remain consistent across various definitions of sequence conservation.
- Approximately one-third of GWAS-associated lincRNAs are nonconserved, rising to two-thirds with stringent conservation criteria.
Conclusions:
- Nonconserved lincRNAs play a significant role in complex cardiometabolic traits.
- The abundance and association patterns of nonconserved lincRNAs challenge traditional prioritization strategies.
- Genomic discoveries in cardiometabolic diseases may require revised approaches considering nonconserved lincRNAs.
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