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Genome-wide association study of lncRNA polymorphisms with bone mineral density.
Annals of Human Genetics 2018 September
Recent studies suggested that long noncoding RNAs (lncRNAs) were widely transcribed in the genome, but their potential roles in the genetic complexity of human disorders required further exploration. The purpose of the present study was to explore genetic polymorphisms of lncRNAs associated with bone mineral density (BMD) and its potential value. Based on the lncRNASNP database, 55,906 lncSNPs were selected to conduct a genome-wide association study meta-analysis among 11,140 individuals of seven independent studies for BMDs at femoral neck (FN), lumbar spine, and total hip (HIP). Promising results were replicated in Genetic Factors for Osteoporosis Consortium (GEFOS Sequencing, n = 32,965). We found two lncRNA loci that were significantly associated with BMD. MEF2C antisense RNA 1 (MEF2C-AS1) located at 5q14.3 was significantly associated with FN-BMD after Bonferroni correction, and the strongest association signal was detected at rs6894139 (P = 3.03 × 10-9 ). LOC100506136 rs6465531 located at 7q21.3 showed significant association with HIP-BMD (P = 7.43 × 10-7 ). MEF2C-AS1 rs6894139 was replicated in GEFOS Sequencing with P-value of 1.43 × 10-23 . Our results illustrated the important role of polymorphisms in lncRNAs in determining variations of BMD and provided justification and evidence for subsequent functional studies.
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