Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline.
Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline.
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DOI：
10.1136/thoraxjnl-2016-208448
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发表时间：
2017-05
期刊：
影响因子：
10
通讯作者：
Tobin MD
中科院分区：
文献类型：
--
作者：
John C;Soler Artigas M;Hui J;Nielsen SF;Rafaels N;Paré PD;Hansel NN;Shrine N;Kilty I;Malarstig A;Jelinsky SA;Vedel-Krogh S;Barnes K;Hall IP;Beilby J;Musk AW;Nordestgaard BG;James A;Wain LV;Tobin MD
全基因组关联研究已经确定了许多影响横截面肺功能的遗传区域。肺功能的纵向下降也包括遗传因素，但遗传决定因素尚未确定。我们的目的是确定与横截面肺功能相关的区域是否也与纵向下降相关，并寻找影响下降的新变体。我们分析了来自布塞尔顿健康研究队列的4167名个体的全基因组数据，这些个体接受了肺量测定（8个时间点的12695个观察结果）。 拟合混合模型，并计算26个已知地区对FEV 1和FEV 1/FVC基线和纵向变化的联合效应的加权风险评分。在两个独立的队列中确定并随访了潜在的其他感兴趣区域。先前与横截面肺功能相关的26个区域共同显示对基线肺功能的强烈影响（对于FEV 1/FVC，p=4.44×10−16），但对纵向下降没有影响（对于FEV 1/FVC，p=0.160）。这在一个独立的队列中重复。确定了39个额外的感兴趣区域（48个变体）;这些关联在另外两个队列中没有重复。先前鉴定的遗传变异共同对成人的横截面肺功能具有强烈的影响，但对肺功能下降的速率几乎没有影响。它们可能通过肺发育影响COPD风险。虽然没有遗传变异在严格的全基因组意义上与肺功能下降相关，但肺功能的纵向变化是可遗传的，这表明未来的发现还有余地。
Genome-wide association studies have identified numerous genetic regions that influence cross-sectional lung function. Longitudinal decline in lung function also includes a heritable component but the genetic determinants have yet to be defined. We aimed to determine whether regions associated with cross-sectional lung function were also associated with longitudinal decline and to seek novel variants which influence decline. We analysed genome-wide data from 4167 individuals from the Busselton Health Study cohort, who had undergone spirometry (12 695 observations across eight time points). A mixed model was fitted and weighted risk scores were calculated for the joint effect of 26 known regions on baseline and longitudinal changes in FEV1 and FEV1/FVC. Potential additional regions of interest were identified and followed up in two independent cohorts. The 26 regions previously associated with cross-sectional lung function jointly showed a strong effect on baseline lung function (p=4.44×10−16 for FEV1/FVC) but no effect on longitudinal decline (p=0.160 for FEV1/FVC). This was replicated in an independent cohort. 39 additional regions of interest (48 variants) were identified; these associations were not replicated in two further cohorts. Previously identified genetic variants jointly have a strong effect on cross-sectional lung function in adults but little or no effect on the rate of decline of lung function. It is possible that they influence COPD risk through lung development. Although no genetic variants have yet been associated with lung function decline at stringent genome-wide significance, longitudinal change in lung function is heritable suggesting that there is scope for future discoveries.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1164/rccm.200402-230oc
发表时间：
2005-01-15
影响因子：
24.7
作者：
James, AL;Palmer, LJ;Musk, AW
通讯作者：
Musk, AW
影响因子：
10
作者：
Afzal, Shoaib;Lange, Peter;Nordestgaard, Borge G.
通讯作者：
Nordestgaard, Borge G.
影响因子：
30.8
作者：
Repapi, Emmanouela;Sayers, Ian;Tobin, Martin D.
通讯作者：
Tobin, Martin D.
不同的基因与颗粒物质和烟草烟雾相互作用，在影响一般人群的肺功能下降时与烟雾烟相互作用。
影响因子：
3.7
作者：
Curjuric I;Imboden M;Nadif R;Kumar A;Schindler C;Haun M;Kronenberg F;Künzli N;Phuleria H;Postma DS;Russi EW;Rochat T;Demenais F;Probst-Hensch NM
通讯作者：
Probst-Hensch NM