A global map for dissecting phenotypic variants in human lincRNAs

Abstract

Large intergenic noncoding RNAs (lincRNAs) are emerging as key factors of multiple cellular processes. Cumulative evidence has linked lincRNA polymorphisms to diverse diseases. However, the global properties of lincRNA polymorphisms and their implications for human disease remain largely unknown. Here we performed a systematic analysis of naturally occurring variants in human lincRNAs, with a particular focus on lincRNA polymorphism as novel risk factor of disease etiology. We found that lincRNAs exhibited a relatively low level of polymorphisms, and low single-nucleotide polymorphism (SNP) density lincRNAs might have a broad range of functions. We also found that some polymorphisms in evolutionarily conserved regions of lincRNAs had significant effects on predicted RNA secondary structures, indicating their potential contribution to diseases. We mapped currently available phenotype-associated SNPs to lincRNAs and found that lincRNAs were associated with a wide range of human diseases. Some lincRNAs could be responsible for particular diseases. Our results provided not only a global perspective on genetic variants in human lincRNAs but also novel insights into the function and etiology of lincRNA. All the data in this study can be accessed and retrieved freely via a web server at

Novel Insights into the Multiple Sclerosis Risk Gene ANKRD55

“…200 nt that do not contain an open reading frame; although their biological meaning and function still need to be elucidated, ample evidence, including specific subcellular localization, tissue specificity, and association with disease, indicates that they may be essential regulators of cell function (27)(28)(29). The importance of lncRNAs in MS is highlighted by recent studies showing that various SNPs associated with MS in GWAS are located in genomic regions that code for lncRNAs (30) or regulate lncRNA expression in cis in human monocytes (31). Abundant expression of ANKRD55 007 in CD4 + T cells may be an indication of the unique cell-specific functional role for this noncoding RNA; it is an intriguing finding that merits further investigation.…”

From Loci to Biology

“…47 A number of studies examined the implication of lincRNAs in complex diseases based on GWAS studies (LincPoly 48 , LincSNP 49 ). These studies represent initial efforts to integrate disease-associated SNPs and human lincRNAs, but both datasets do not include complete GWAS SNP data, and focus on only a few thousand lincRNAs.…”

Long Non-coding RNAs: Novel Targets for Nervous System Disease Diagnosis and Therapy

“…For example, rs6475606, rs564398 and rs496892, rs1063192, and rs2151280 modify susceptibility to intracranial aneurysm, large-vessel ischemic stroke, glioma, and plexiform neurofibroma, respectively. Other correlations between lncRNA polymorphisms and disease are actively being investigated [79]. One study analyzed data from the Alzheimer Disease (AD) Neuroimaging Initiative and reported that the rs7990916:T> C polymorphism in the brain-specific, rapidly evolving lincRNA, TCONS_00021856/linc-SLITRK5-11, is associated with regional cortical gray matter volumes in normal controls and in patients with mild cognitive impairment and AD [80].…”