在非裔美国家庭中，通过混合映射和精细映射分析确定的高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）和甘油三酯的变异体。

Variants for HDL-C, LDL-C, and triglycerides identified from admixture mapping and fine-mapping analysis in African American families.

作者信息

Shetty Priya B, Tang Hua, Feng Tao, Tayo Bamidele, Morrison Alanna C, Kardia Sharon L R, Hanis Craig L, Arnett Donna K, Hunt Steven C, Boerwinkle Eric, Rao Dabeeru C, Cooper Richard S, Risch Neil, Zhu Xiaofeng

机构信息

From the Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH (P.B.S., T.F., X.Z.); Department of Genetics, Stanford University School of Medicine, Stanford, CA (H.T.); Department of Public Health Sciences, Loyola University of Chicago Stritch School of Medicine, Maywood, IL (B.T., R.S.C.); Division of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas Health Science Center at Houston School of Public Health (A.C.M., C.L.H., E.B.); Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor (S.L.R.K.); Department of Epidemiology, University of Alabama at Birmingham School of Public Health (D.K.A.); Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (S.C.H.); Division of Biostatistics, Washington University in St. Louis School of Medicine, St. Louis, MO (D.C. Rao); and Department of Epidemiology and Biostatistics, University of California, San Francisco (N.R.).

出版信息

Circ Cardiovasc Genet. 2015 Feb;8(1):106-13. doi: 10.1161/CIRCGENETICS.114.000481. Epub 2014 Dec 31.

DOI:10.1161/CIRCGENETICS.114.000481

PMID:25552592

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4378661/

Abstract

BACKGROUND

Admixture mapping of lipids was followed-up by family-based association analysis to identify variants for cardiovascular disease in African Americans.

METHODS AND RESULTS

The present study conducted admixture mapping analysis for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. The analysis was performed in 1905 unrelated African American subjects from the National Heart, Lung and Blood Institute's Family Blood Pressure Program (FBPP). Regions showing admixture evidence were followed-up with family-based association analysis in 3556 African American subjects from the FBPP. The admixture mapping and family-based association analyses were adjusted for age, age(2), sex, body mass index, and genome-wide mean ancestry to minimize the confounding caused by population stratification. Regions that were suggestive of local ancestry association evidence were found on chromosomes 7 (low-density lipoprotein cholesterol), 8 (high-density lipoprotein cholesterol), 14 (triglycerides), and 19 (total cholesterol and triglycerides). In the fine-mapping analysis, 52 939 single-nucleotide polymorphisms (SNPs) were tested and 11 SNPs (8 independent SNPs) showed nominal significant association with high-density lipoprotein cholesterol (2 SNPs), low-density lipoprotein cholesterol (4 SNPs), and triglycerides (5 SNPs). The family data were used in the fine-mapping to identify SNPs that showed novel associations with lipids and regions, including genes with known associations for cardiovascular disease.

CONCLUSIONS

This study identified regions on chromosomes 7, 8, 14, and 19 and 11 SNPs from the fine-mapping analysis that were associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides for further studies of cardiovascular disease in African Americans.

摘要

背景

对脂质进行混合映射分析后，通过基于家系的关联分析来确定非裔美国人中与心血管疾病相关的变异。

方法与结果

本研究对总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和甘油三酯进行了混合映射分析。分析在来自美国国立心肺血液研究所家庭血压项目（FBPP）的1905名无亲缘关系的非裔美国受试者中进行。对显示混合证据的区域，在来自FBPP的3556名非裔美国受试者中进行基于家系的关联分析随访。混合映射和基于家系的关联分析针对年龄、年龄的平方、性别、体重指数和全基因组平均祖先进行了调整，以尽量减少人群分层造成的混杂。在7号染色体（低密度脂蛋白胆固醇）、8号染色体（高密度脂蛋白胆固醇）、14号染色体（甘油三酯）和19号染色体（总胆固醇和甘油三酯）上发现了提示本地祖先关联证据的区域。在精细定位分析中，测试了52939个单核苷酸多态性（SNP），11个SNP（8个独立SNP）与高密度脂蛋白胆固醇（2个SNP）、低密度脂蛋白胆固醇（4个SNP）和甘油三酯（5个SNP）显示出名义上的显著关联。家系数据用于精细定位，以识别与脂质和区域显示新关联的SNP，包括与心血管疾病有已知关联的基因。