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Edited by C. Thomas Caskey, Baylor College of Medicine, Houston, TX, and approved January 15, 2015 (received for review August 12, 2014)
Article Figures & SI
Figures
- Fig. 1.
MEGHA SNP-based heritability estimates for global morphometric measurements are plotted against GCTA results.
- Fig. 2.
Evaluation of MEGHA using average cortical thickness measures in 68 regions of interest (ROIs). MEGHA SNP-based heritability estimates (Left) and P values (Right) are plotted against GCTA results for each ROI. There is an excellent concordance between MEGHA and GCTA.
- Fig. 3.
Superior (S), inferior (I), lateral (L), anterior (A), posterior (P), and medial (M) views of the vertex-wise surface maps for SNP-based heritability significance of cortical thickness measures constructed by MEGHA. All clusters identified with a cluster-forming threshold P = 0.01 are shown. Five clusters that are familywise error corrected (FWEc) significant in size (FWEc, P < 0.05) based on 1,000 permutations are white outlined and annotated.
Tables
Measurement Test–retest reliability GCTA MEGHA SE P value FWEc P value (Bonf) P value Perm P value FWEc P value (Perm) Intracranial volume (ICV) 0.995 0.849 0.275 6.95E-4 0.011 0.804 3.91E-4 4.16E-4 4.21E-3 Total brain volume 0.997 0.981 0.273 1.07E-4 1.71E-3 0.929 5.24E-5 7.00E-5 6.32E-4 Left hemispheric cortical GM volume 0.992 0.521 0.279 0.033 0.529 0.432 0.036 0.036 0.265 Right hemispheric cortical GM volume 0.991 0.492 0.279 0.041 0.652 0.411 0.043 0.043 0.307 Total cortical GM volume 0.994 0.515 0.279 0.034 0.550 0.429 0.037 0.037 0.270 Total subcortical GM volume 0.968 0.357 0.279 0.104 1.000 0.298 0.107 0.107 0.587 Total GM volume 0.995 0.475 0.279 0.050 0.796 0.382 0.055 0.055 0.374 Left hemispheric WM volume 0.996 0.416 0.279 0.071 1.000 0.344 0.075 0.076 0.467 Right hemispheric WM volume 0.996 0.302 0.279 0.140 1.000 0.257 0.141 0.142 0.691 Total WM volume 0.996 0.369 0.279 0.095 1.000 0.310 0.098 0.098 0.556 Left hemispheric mean cortical thickness 0.899 0.688 0.277 5.60E-3 0.090 0.625 4.54E-3 4.83E-3 0.043 Right hemispheric mean cortical thickness 0.885 0.732 0.277 3.48E-3 0.056 0.662 2.84E-3 2.99E-3 0.027 Overall mean cortical thickness 0.935 0.734 0.277 3.41E-3 0.055 0.665 2.73E-3 2.93E-3 0.027 Left hemispheric total surface area 0.999 0.298 0.279 0.137 1.000 0.270 0.130 0.129 0.658 Right hemispheric total surface area 0.997 0.288 0.279 0.139 1.000 0.274 0.127 0.126 0.650 Total surface area 0.998 0.305 0.279 0.128 1.000 0.283 0.118 0.118 0.625 Test–retest reliability of the measurements measured by correlation coefficient is computed using 42 individuals with repeated brain structural MRI scans on separate days. The heritability estimate
- Table 2.
Comparison of the computational time of MEGHA and GCTA when applied to different types of analyses
Case Type of analysis Effective no. of phenotypes GCTA MEGHA 1 Analysis of global morphometric measurements 16 120 s 0.65 s 2 ROI analysis 68 400 s 0.75 s 3 Vertex-wise heritability mapping 299,881 39.01 d 90 s 4 ROI analysis with permutation inference (one million permutations) 68,000,000 24.24 y* 3.5 h 5 Vertex-wise analysis with cluster inference (one thousand permutations) 299,881,000 106.88 y* 6.8 h ↵* Estimated computational time, using the average computational time, ∼11.24 s, for each phenotype in case 3.
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Massively expedited heritability analysis
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