Framingham Heart Study genome-wide association: results for pulmonary function measures.
Framingham Heart Study genome-wide association: results for pulmonary function measures.
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DOI：
10.1186/1471-2350-8-s1-s8
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发表时间：
2007-09-19
影响因子：
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通讯作者：
O'Connor, George T.
中科院分区：
文献类型：
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作者：
Wilk, Jemma B.;Walter, Robert E.;Laramie, Jason M.;Gottlieb, Daniel J.;O'Connor, George T.
通过肺量测定法获得的肺功能测量值用于诊断慢性阻塞性肺疾病（COPD），并且具有高度遗传性。我们进行了全基因组关联（GWA）分析（Affyestival 100 K SNP基因芯片），以测量心脏功能研究中的肺功能。检测了10种肺功能测定表型，包括预测指标的百分比、两次检查的平均肺功能测定指标、基于1秒用力呼气量（FEV 1）、用力肺活量（FVC）、第25 - 75百分位用力呼气流量（FEF 25 -75）、FEV 1/FVC比值和FEF 25 -75/FVC比值的变化率。预测表型的百分比是使用每个参与者的最新肺量测定检查创建的。预测肺功能是使用在健康的从不吸烟者中定义的模型来估计的，并且创建了针对吸烟状态、包年和体重指数（BMI）进行调整的百分比预测测量的标准化残差。所有建模均按性别和队列分层进行。使用两次检查的数据并调整年龄、BMI、身高、吸烟和包年数，创建平均肺量测定表型。肺功能随时间的变化进行了研究，使用两到四次肺功能测定法检查，以计算斜率，然后调整年龄，身高，吸烟和包年。分析仅限于70，987个常染色体SNP，次要等位基因频率≥ 10%，基因型调用率≥ 80%，Hardy-Weinberg平衡p值≥ 0.001。1号染色体上白细胞介素6受体（IL 6 R）的SNP是预测FEF 25 -75百分比的最佳结果。10号染色体上谷胱甘肽S-转移酶ω 2（GSTO 2）的非同义编码SNP在研究两次检查的平均FEV 1和FVC测量值时具有最高排名的结果。SOD 3和维生素D结合蛋白基因（COPD的候选基因）附近的SNP与预测表型百分比相关。GSTO 2和IL 6 R是GWA确定的与肺功能相关的可靠候选基因。这些和其他观察到的关联值得复制研究。肺功能测量的GWA结果资源可在http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?上公开获取id=phs000007。
Pulmonary function measures obtained by spirometry are used to diagnose chronic obstructive pulmonary disease (COPD) and are highly heritable. We conducted genome-wide association (GWA) analyses (Affymetrix 100K SNP GeneChip) for measures of lung function in the Framingham Heart Study. Ten spirometry phenotypes including percent of predicted measures, mean spirometry measures over two examinations, and rates of change based on forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow from the 25th to 75th percentile (FEF25–75), the FEV1/FVC ratio, and the FEF25–75/FVC ratio were examined. Percent predicted phenotypes were created using each participant's latest exam with spirometry. Predicted lung function was estimated using models defined in the set of healthy never-smokers, and standardized residuals of percent predicted measures were created adjusting for smoking status, pack-years, and body mass index (BMI). All modeling was performed stratified by sex and cohort. Mean spirometry phenotypes were created using data from two examinations and adjusting for age, BMI, height, smoking and pack-years. Change in pulmonary function over time was studied using two to four examinations with spirometry to calculate slopes, which were then adjusted for age, height, smoking and pack-years. Analyses were restricted to 70,987 autosomal SNPs with minor allele frequency ≥ 10%, genotype call rate ≥ 80%, and Hardy-Weinberg equilibrium p-value ≥ 0.001. A SNP in the interleukin 6 receptor (IL6R) on chromosome 1 was among the best results for percent predicted FEF25–75. A non-synonymous coding SNP in glutathione S-transferase omega 2 (GSTO2) on chromosome 10 had top-ranked results studying the mean FEV1 and FVC measurements from two examinations. SNPs nearby the SOD3 and vitamin D binding protein genes, candidate genes for COPD, exhibited association to percent predicted phenotypes. GSTO2 and IL6R are credible candidate genes for association to pulmonary function identified by GWA. These and other observed associations warrant replication studies. This resource of GWA results for pulmonary function measures is publicly available at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.