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10.1093/hmg/ddw154

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C5181595!5181595!27288454
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suck abstract from ncbi


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pmid27288454      Hum+Mol+Genet 2016 ; 25 (14): 3125-41
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  • Genome-wide interrogation reveals hundreds of long intergenic noncoding RNAs that associate with cardiometabolic traits #MMPMID27288454
  • Ballantyne RL; Zhang X; Nuñez S; Xue C; Zhao W; Reed E; Salaheen D; Foulkes AS; Li M; Reilly MP
  • Hum Mol Genet 2016[Jul]; 25 (14): 3125-41 PMID27288454show ga
  • Long intergenic noncoding RNAs (lincRNAs) play important roles in disease, but the vast majority of these transcripts remain uncharacterized. We defined a set of 54 944 human lincRNAs by drawing on four publicly available lincRNA datasets, and annotated ?2.5 million single nucleotide polymorphisms (SNPs) from each of 15 cardiometabolic genome-wide association study datasets into these lincRNAs. We identified hundreds of lincRNAs with at least one trait-associated SNP: 898 SNPs in 343 unique lincRNAs at 5% false discovery rate, and 469 SNPs in 146 unique lincRNAs meeting Bonferroni-corrected P < 0.05. An additional 64 trait-associated lincRNAs were identified using a class-level testing strategy at Bonferroni-corrected P < 0.05. To better understand the genomic context and prioritize trait-associated lincRNAs, we examined the pattern of linkage disequilibrium between SNPs in the lincRNAs and SNPs that met genome-wide-significance in the region (±500 kb of lincRNAs). A subset of the lincRNA-trait association findings was replicated in independent Genome-wide association studies data from the Pakistan Risk of Myocardial Infarction Study study. For trait-associated lincRNAs, we also investigated synteny and conservation relative to mouse, expression patterns in five cardiometabolic-relevant tissues, and allele-specific expression in RNA sequencing data for adipose tissue and leukocytes. Finally, we revealed a functional role in human adipocytes for linc-NFE2L3-1, which is expressed in adipose and is associated with waist-hip ratio adjusted for BMI. This comprehensive profile of trait-associated lincRNAs provides novel insights into disease mechanism and serves as a launching point for interrogation of the biology of specific lincRNAs in cardiometabolic disease.
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