Genome-wide association with bone mass and geometry in the Framingham Heart Study

BACKGROUND:Osteoporosis is characterized by low bone mass and compromised bone structure, heritable traits that contribute to fracture risk. There have been no genome-wide association and linkage studies for these traits using high-density genotyping platforms.METHODS:We used the Affymetrix 100K SNP GeneChip marker set in the Framingham Heart Study (FHS) to examine genetic associations with ten primary quantitative traits: bone mineral density (BMD), calcaneal ultrasound, and geometric indices of the hip. To test associations with multivariable-adjusted residual trait values, we used additive generalized estimating equation (GEE) and family-based association tests (FBAT) models within each sex as well as sexes combined. We evaluated 70,987 autosomal SNPs with genotypic call rates [greater than or equal to]80%, HWE p [greater than or equal to] 0.001, and MAF [greater than or equal to]10% in up to 1141 phenotyped individuals (495 men and 646 women, mean age 62.5 yrs). Variance component linkage analysis was performed using 11,200 markers.RESULTS:Heritability estimates for all bone phenotypes were 30-66%. LOD scores [greater than or equal to]3.0 were found on chromosomes 15 (1.5 LOD confidence interval: 51,336,679-58,934,236 bp) and 22 (35,890,398-48,603,847 bp) for femoral shaft section modulus. The ten primary phenotypes had 12 associations with 100K SNPs in GEE models at p < 0.000001 and 2 associations in FBAT models at p < 0.000001. The 25 most significant p-values for GEE and FBAT were all less than 3.5 x 10-6 and 2.5 x 10-5, respectively. Of the 40 top SNPs with the greatest numbers of significantly associated BMD traits (including femoral neck, trochanter, and lumbar spine), one half to two-thirds were in or near genes that have not previously been studied for osteoporosis. Notably, pleiotropic associations between BMD and bone geometric traits were uncommon. Evidence for association (FBAT or GEE p < 0.05) was observed for several SNPs in candidate genes for osteoporosis, such as rs1801133 in MTHFR; rs1884052 and rs3778099 in ESR1; rs4988300 in LRP5; rs2189480 in VDR; rs2075555 in COLIA1; rs10519297 and rs2008691 in CYP19, as well as SNPs in PPARG (rs10510418 and rs2938392) and ANKH (rs2454873 and rs379016). All GEE, FBAT and linkage results are provided as an open-access results resource at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.CONCLUSION:The FHS 100K SNP project offers an unbiased genome-wide strategy to identify new candidate loci and to replicate previously suggested candidate genes for osteoporosis.

Stochastic Mesh-Based Multiview Reconstruction

A method for reconstruction of 3D polygonal models from multiple views is presented. The method uses sampling techniques to construct a texture-mapped semi-regular polygonal mesh of the object in question. Given a set of views and segmentation of the object in each view, constructive solid geometry is used to build a visual hull from silhouette prisms. The resulting polygonal mesh is simplified and subdivided to produce a semi-regular mesh. Regions of model fit inaccuracy are found by projecting the reference images onto the mesh from different views. The resulting error images for each view are used to compute a probability density function, and several points are sampled from it. Along the epipolar lines corresponding to these sampled points, photometric consistency is evaluated. The mesh surface is then pulled towards the regions of higher photometric consistency using free-form deformations. This sampling-based approach produces a photometrically consistent solution in much less time than possible with previous multi-view algorithms given arbitrary camera placement.

Head Tracking via Robust Registration in Texture Map Images

A novel method for 3D head tracking in the presence of large head rotations and facial expression changes is described. Tracking is formulated in terms of color image registration in the texture map of a 3D surface model. Model appearance is recursively updated via image mosaicking in the texture map as the head orientation varies. The resulting dynamic texture map provides a stabilized view of the face that can be used as input to many existing 2D techniques for face recognition, facial expressions analysis, lip reading, and eye tracking. Parameters are estimated via a robust minimization procedure; this provides robustness to occlusions, wrinkles, shadows, and specular highlights. The system was tested on a variety of sequences taken with low quality, uncalibrated video cameras. Experimental results are reported.

Fast, Reliable Head Tracking under Varying Illumination: An Approach Based on Registration of Texture-Mapped 3D Model

An improved technique for 3D head tracking under varying illumination conditions is proposed. The head is modeled as a texture mapped cylinder. Tracking is formulated as an image registration problem in the cylinder's texture map image. The resulting dynamic texture map provides a stabilized view of the face that can be used as input to many existing 2D techniques for face recognition, facial expressions analysis, lip reading, and eye tracking. To solve the registration problem in the presence of lighting variation and head motion, the residual error of registration is modeled as a linear combination of texture warping templates and orthogonal illumination templates. Fast and stable on-line tracking is achieved via regularized, weighted least squares minimization of the registration error. The regularization term tends to limit potential ambiguities that arise in the warping and illumination templates. It enables stable tracking over extended sequences. Tracking does not require a precise initial fit of the model; the system is initialized automatically using a simple 2D face detector. The only assumption is that the target is facing the camera in the first frame of the sequence. The formulation is tailored to take advantage of texture mapping hardware available in many workstations, PC's, and game consoles. The non-optimized implementation runs at about 15 frames per second on a SGI O2 graphic workstation. Extensive experiments evaluating the effectiveness of the formulation are reported. The sensitivity of the technique to illumination, regularization parameters, errors in the initial positioning and internal camera parameters are analyzed. Examples and applications of tracking are reported.

A Neural Model of 3D Shape-From-Texture: Multiple-Scale Filtering, Boundary Grouping, and Surface Filling-In

A neural model is presented of how cortical areas V1, V2, and V4 interact to convert a textured 2D image into a representation of curved 3D shape. Two basic problems are solved to achieve this: (1) Patterns of spatially discrete 2D texture elements are transformed into a spatially smooth surface representation of 3D shape. (2) Changes in the statistical properties of texture elements across space induce the perceived 3D shape of this surface representation. This is achieved in the model through multiple-scale filtering of a 2D image, followed by a cooperative-competitive grouping network that coherently binds texture elements into boundary webs at the appropriate depths using a scale-to-depth map and a subsequent depth competition stage. These boundary webs then gate filling-in of surface lightness signals in order to form a smooth 3D surface percept. The model quantitatively simulates challenging psychophysical data about perception of prolate ellipsoids (Todd and Akerstrom, 1987, J. Exp. Psych., 13, 242). In particular, the model represents a high degree of 3D curvature for a certain class of images, all of whose texture elements have the same degree of optical compression, in accordance with percepts of human observers. Simulations of 3D percepts of an elliptical cylinder, a slanted plane, and a photo of a golf ball are also presented.

Texture Segregation By Visual Cortex: Perceptual Grouping, Attention, and Learning

A neural model is proposed of how laminar interactions in the visual cortex may learn and recognize object texture and form boundaries. The model brings together five interacting processes: region-based texture classification, contour-based boundary grouping, surface filling-in, spatial attention, and object attention. The model shows how form boundaries can determine regions in which surface filling-in occurs; how surface filling-in interacts with spatial attention to generate a form-fitting distribution of spatial attention, or attentional shroud; how the strongest shroud can inhibit weaker shrouds; and how the winning shroud regulates learning of texture categories, and thus the allocation of object attention. The model can discriminate abutted textures with blurred boundaries and is sensitive to texture boundary attributes like discontinuities in orientation and texture flow curvature as well as to relative orientations of texture elements. The model quantitatively fits a large set of human psychophysical data on orientation-based textures. Object boundar output of the model is compared to computer vision algorithms using a set of human segmented photographic images. The model classifies textures and suppresses noise using a multiple scale oriented filterbank and a distributed Adaptive Resonance Theory (dART) classifier. The matched signal between the bottom-up texture inputs and top-down learned texture categories is utilized by oriented competitive and cooperative grouping processes to generate texture boundaries that control surface filling-in and spatial attention. Topdown modulatory attentional feedback from boundary and surface representations to early filtering stages results in enhanced texture boundaries and more efficient learning of texture within attended surface regions. Surface-based attention also provides a self-supervising training signal for learning new textures. Importance of the surface-based attentional feedback in texture learning and classification is tested using a set of textured images from the Brodatz micro-texture album. Benchmark studies vary from 95.1% to 98.6% with attention, and from 90.6% to 93.2% without attention.

Preattentive Texture Segmentation and Grouping by the Boundary Contour System

An improved Boundary Contour System (BCS) neural network model of preattentive vision is applied to two images that produce strong "pop-out" of emergent groupings in humans. In humans these images generate groupings collinear with or perpendicular to image contrasts. Analogous groupings occur in computer simulations of the model. Long-range cooperative and short-range competitive processes of the BCS dynamically form the stable groupings of texture regions in response to the images.