Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression.
Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression.
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DOI：
10.3389/fnins.2012.00115
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发表时间：
2012
影响因子：
4.3
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Kohannim O;Hibar DP;Stein JL;Jahanshad N;Hua X;Rajagopalan P;Toga AW;Jack CR Jr;Weiner MW;de Zubicaray GI;McMahon KL;Hansell NK;Martin NG;Wright MJ;Thompson PM;Alzheimer’s Disease Neuroimaging Initiative
我们采用最小绝对收缩和选择算子（LASSO）回归来评估脑图像全基因组关联研究（GWAS）中的基因效应，使用来自729名受试者的mri颞叶体积测量，作为阿尔茨海默病神经影像学倡议（ADNI）的一部分进行扫描。LASSO选择了单个基因中的稀疏snp组，从而识别影响数据的有效变体集。在评估这些snp与神经影像学指标的相关性时，将它们联合考虑。我们发现22个基因在影响颞叶体积方面具有全基因组意义。与标准的单变量GWAS相比，显著基因的数量大大增加。这些顶级基因都在大脑中表达，包括先前与脑功能或神经精神疾病相关的基因，如MACROD2、SORCS2、GRIN2B、MAGI2、NPAS3、CLSTN2、GABRG3、NRXN3、PRKAG2、GAS7、RBFOX1、ADARB2、CHD4和CDH13。我们用这种方法鉴定的顶级基因也对颞叶的体素、基于张量的形态测量（TBM）图谱显示出显著而广泛的后期效应。最显著的相关基因是名为MACROD2的自闭症易感基因。我们成功地复制了MACROD2基因对564名年轻的澳大利亚健康成年双胞胎和兄弟姐妹的影响，并进行了MRI扫描（平均年龄：23.8±2.2 SD年）。我们的方法有力地补充了检测基因对活脑影响的单变量技术。
We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2. We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8 ± 2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain.
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影响因子：
1.3
作者：
COLLINS, DL;NEELIN, P;EVANS, AC
通讯作者：
EVANS, AC
影响因子：
5.7
作者：
Chen, Kewei;Langbaum, Jessica B. S.;Fleisher, Adam S.;Ayutyanont, Napatkamon;Reschke, Cole;Lee, Wendy;Liu, Xiaofen;Bandy, Dan;Alexander, Gene E.;Thompson, Paul M.;Foster, Norman L.;Harvey, Danielle J.;de Leon, Mony J.;Koeppe, Robert A.;Jagust, William J.;Weiner, Michael W.;Reiman, Eric M.
通讯作者：
Reiman, Eric M.
影响因子：
2.7
作者：
Abraham R;Moskvina V;Sims R;Hollingworth P;Morgan A;Georgieva L;Dowzell K;Cichon S;Hillmer AM;O'Donovan MC;Williams J;Owen MJ;Kirov G
通讯作者：
Kirov G
影响因子：
--
作者：
Chen, Han;Hendricks, Audrey E;Liu, Ching-Ti
通讯作者：
Liu, Ching-Ti
DOI：
10.1523/jneurosci.5794-10.2011
发表时间：
2011-05-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Braskie MN;Jahanshad N;Stein JL;Barysheva M;McMahon KL;de Zubicaray GI;Martin NG;Wright MJ;Ringman JM;Toga AW;Thompson PM
通讯作者：
Thompson PM