Fine genetic mapping of the chromosome 11q23.3 region in a Han Chinese population:insights into the apolipoprotein genes underlying the blood lipid-lipoprotein variances  

作　　者：Weihua Shou Chenhui Zhang Jinxiu Shi Hong Wu Wei Huan 

机构地区：[1]Department of Genetics,Shanghai-MOST Key Laboratory of Health and Disease Genomics,Chinese National Human Genome Center at Shanghai and Shanghai Academy of Science and Technology,Shanghai 200025,China [2]Department of Cardiology,Changhai Hospital,The Second Military Medical University,Shanghai 200433,China

出　　处：《Journal of Genetics and Genomics》2020年第12期756-769,共14页遗传学报（英文版）

基　　金：We gratefully acknowledge all the contributors that made this research possible,all the sample donors for this study,and all the clinicians for their assistance in recruiting participants to the study.This work was supported by the grant from the National Natural Science Foundation of China(31401082).

摘　　要：The unusual chromosome 11q23.3 harboring the apolipoprotein(APO)gene cluster has been well documented for its essential roles in plasma lipid-related traits and atherosclerotic cardiovascular diseases.However,its genetic architecture and the potential biological mechanisms underlying complex phenotypes have not been well assessed.We conducted a study for this target region in a Han Chinese population through a stepwise forward framework based on massive parallel sequencing,association analyses,genetic fine mapping,and functional interpretation.The present study identified new meaningful genetic associations that were not simply determined by statistical significance.In addition to the APOA5 gene,we found robust evidence of the genetic commitments of APOC3 and APOA1 to blood lipids.Several variants with high confidence were prioritized along with the potential biological mechanism interpretations in the wake of adaptive fine-mapping analyses.rs2849174 in the APOC3 enhancer was discovered with an unrivaled posterior probability of causality for triglyceride levels and could mediate APOC3 expression through enhancer activity modulated by a combination of histone modifications and transcription factor accessibility.Similarly,multiple lines of evidence converged in favor of rs3741297 as a causal variant influencing high-density lipoprotein cholesterol.Our findings provided novel insights into this genomic locus in the Chinese population.

关 键 词：APO gene cluster Blood lipids Coronary artery disease Genetic associations Progressive analyses for prioritizing Causal genetic factors 

分 类 号：R394[医药卫生—医学遗传学]