Parker Margaret M, Foreman Marilyn G, Abel Haley J, Mathias Rasika A, Hetmanski Jacqueline B, Crapo James D, Silverman Edwin K, Beaty Terri H
Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland, United States of America.
Genet Epidemiol. 2014 Nov;38(7):652-9. doi: 10.1002/gepi.21847. Epub 2014 Aug 11.
African Americans are admixed with genetic contributions from European and African ancestral populations. Admixture mapping leverages this information to map genes influencing differential disease risk across populations. We performed admixture and association mapping in 3,300 African American current or former smokers from the COPDGene Study. We analyzed estimated local ancestry and SNP genotype information to identify regions associated with FEV1 /FVC, the ratio of forced expiratory volume in one second to forced vital capacity, measured by spirometry performed after bronchodilator administration. Global African ancestry inversely associated with FEV1 /FVC (P = 0.035). Genome-wide admixture analysis, controlling for age, gender, body mass index, current smoking status, pack-years smoked, and four principal components summarizing the genetic background of African Americans in the COPDGene Study, identified a region on chromosome 12q14.1 associated with FEV1 /FVC (P = 2.1 × 10(-6) ) when regressed on local ancestry. Allelic association in this region of chromosome 12 identified an intronic variant in FAM19A2 (rs348644) as associated with FEV1 /FVC (P = 1.76 × 10(-6) ). By combining admixture and association mapping, a marker on chromosome 12q14.1 was identified as being associated with reduced FEV1 /FVC ratio among African Americans in the COPDGene Study.
非裔美国人混合了来自欧洲和非洲祖先群体的基因贡献。混合映射利用这些信息来绘制影响不同人群疾病风险差异的基因图谱。我们在慢性阻塞性肺疾病基因研究(COPDGene Study)的3300名非裔美国现吸烟者或 former smokers中进行了混合和关联映射。我们分析了估计的局部血统和单核苷酸多态性(SNP)基因型信息,以确定与一秒用力呼气容积(FEV1)/用力肺活量(FVC)相关的区域,FEV1/FVC是指在使用支气管扩张剂后通过肺活量测定法测量的一秒用力呼气容积与用力肺活量的比值。全球非洲血统与FEV1/FVC呈负相关(P = 0.035)。在控制了年龄、性别、体重指数、当前吸烟状态、吸烟包年数以及总结COPDGene研究中非裔美国人遗传背景的四个主要成分后,全基因组混合分析在对局部血统进行回归时,确定了12号染色体q14.1区域与FEV1/FVC相关(P = 2.1×10^(-6))。12号染色体该区域的等位基因关联确定FAM19A2基因中的一个内含子变异(rs348644)与FEV1/FVC相关(P = 1.76×10^(-6))。通过结合混合和关联映射,在COPDGene研究中确定了12号染色体q14.1上的一个标记与非裔美国人中降低的FEV1/FVC比值相关。