Genetic analysis of cortical thickness and fractional anisotropy of water diffusion in the brain.
Genetic analysis of cortical thickness and fractional anisotropy of water diffusion in the brain.
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DOI：
10.3389/fnins.2011.00120
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发表时间：
2011
影响因子：
4.3
通讯作者：
Blangero J
中科院分区：
文献类型：
--
作者：
Kochunov P;Glahn DC;Nichols TE;Winkler AM;Hong EL;Holcomb HH;Stein JL;Thompson PM;Curran JE;Carless MA;Olvera RL;Johnson MP;Cole SA;Kochunov V;Kent J;Blangero J
目的：大脑皮质灰质（GM）的厚度和大脑白色物质（WM）的各向异性分数（FA）均随年龄呈倒U形变化。这两个措施是正相关的，并可能受到共同的生物机制。我们采用了四种类型的遗传分析，以本地化个别基因的多效性后，这些表型。研究方法：全脑和局部GM厚度和FA值是从712名墨西哥裔美国参与者（438名女性，年龄= 47.9 ± 13.2岁）的高分辨率解剖和扩散张量MR图像中测量的，这些参与者来自73个（9.7 ± 9.3个人/家庭）大家庭。两个性状之间的相关性的显着性估计使用双变量遗传相关分析。使用全基因组数量性状基因座（QTL）分析的染色体区域，共同影响这两个性状的本地化。使用Illumina 1 M芯片上的SNP基因分型和与基于白细胞的基因表达分析的相关性进行基因定位。使用Illumina BeadChip测量基因表达。371例受试者的这些数据可用。结果：GM厚度与FA值之间存在显著的遗传相关。优势对数显著（LOD ≥ 3.0）的QTL定位于染色体15 q22 -23。更详细的定位报告显示，位于QTL内的1565个SNP没有显著关联（p < 5·10−5）。事后分析表明，40%的潜在显著（p ≤ 10−3）SNP定位于相关孤儿受体α（RORA）和NARG 2基因。据报道，rs 2456930多态性与阿尔茨海默病神经影像学倡议受试者中的一项重要GWAS发现存在潜在的显着关联。RORA和ADAM 10基因的表达水平与FA和GM厚度均显著相关（p < 0.05）。NARG 2表达与GM厚度显著相关（p < 0.05），但未显示与FA显著相关（p = 0.09）。讨论：本研究在15 q22 -23处鉴定了一个新的显著QTL。SNP与基因表达分析的相关性表明，RORA，NARG 2和ADAM 10共同影响GM厚度和WM-FA值。
Objectives: The thickness of the brain’s cortical gray matter (GM) and the fractional anisotropy (FA) of the cerebral white matter (WM) each follow an inverted U-shape trajectory with age. The two measures are positively correlated and may be modulated by common biological mechanisms. We employed four types of genetic analyses to localize individual genes acting pleiotropically upon these phenotypes. Methods: Whole-brain and regional GM thickness and FA values were measured from high-resolution anatomical and diffusion tensor MR images collected from 712, Mexican American participants (438 females, age = 47.9 ± 13.2 years) recruited from 73 (9.7 ± 9.3 individuals/family) large families. The significance of the correlation between two traits was estimated using a bivariate genetic correlation analysis. Localization of chromosomal regions that jointly influenced both traits was performed using whole-genome quantitative trait loci (QTL) analysis. Gene localization was performed using SNP genotyping on Illumina 1M chip and correlation with leukocyte-based gene-expression analyses. The gene-expressions were measured using the Illumina BeadChip. These data were available for 371 subjects. Results: Significant genetic correlation was observed among GM thickness and FA values. Significant logarithm of odds (LOD ≥ 3.0) QTLs were localized within chromosome 15q22–23. More detailed localization reported no significant association (p < 5·10−5) for 1565 SNPs located within the QTLs. Post hoc analysis indicated that 40% of the potentially significant (p ≤ 10−3) SNPs were localized to the related orphan receptor alpha (RORA) and NARG2 genes. A potentially significant association was observed for the rs2456930 polymorphism reported as a significant GWAS finding in Alzheimer’s disease neuroimaging initiative subjects. The expression levels for RORA and ADAM10 genes were significantly (p < 0.05) correlated with both FA and GM thickness. NARG2 expressions were significantly correlated with GM thickness (p < 0.05) but failed to show a significant correlation (p = 0.09) with FA. Discussion: This study identified a novel, significant QTL at 15q22–23. SNP correlation with gene-expression analyses indicated that RORA, NARG2, and ADAM10 jointly influence GM thickness and WM–FA values.
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影响因子：
5.7
作者：
Chiang MC;McMahon KL;de Zubicaray GI;Martin NG;Hickie I;Toga AW;Wright MJ;Thompson PM
通讯作者：
Thompson PM
影响因子：
2.9
作者：
Edenberg HJ;Bierut LJ;Boyce P;Cao M;Cawley S;Chiles R;Doheny KF;Hansen M;Hinrichs T;Jones K;Kelleher M;Kennedy GC;Liu G;Marcus G;McBride C;Murray SS;Oliphant A;Pettengill J;Porjesz B;Pugh EW;Rice JP;Rubano T;Shannon S;Steeke R;Tischfield JA;Tsai YY;Zhang C;Begleiter H
通讯作者：
Begleiter H
影响因子：
30.8
作者：
Goering, Harald H. H.;Curran, Joanne E.;Blangero, John
通讯作者：
Blangero, John
影响因子：
30.8
作者：
Burdick, Joshua T.;Chen, Wei-Min;Cheung, Vivian G.
通讯作者：
Cheung, Vivian G.
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR