Applications of machine learning and data mining methods to detect associations of rare and common variants with complex traits.

Machine learning methods (MLMs), designed to develop models using high-dimensional predictors, have been used to analyze genome-wide genetic and genomic data to predict risks for complex traits. We summarize the results from six contributions to our Genetic Analysis Workshop 18 working group; these investigators applied MLMs and data mining to analyses of rare and common genetic variants measured in pedigrees. To develop risk profiles, group members analyzed blood pressure traits along with single-nucleotide polymorphisms and rare variant genotypes derived from sequence and imputation analyses in large Mexican American pedigrees.

Support for calcium channel gene defects in autism spectrum disorders.

Background: Alternation of synaptic homeostasis is a biological process whose disruption might predispose children to autism spectrum disorders (ASD). Calcium channel genes (CCG) contribute to modulating neuronal function and evidence implicating CCG in ASD has been accumulating. We conducted a targeted association analysis of CCG using existing genome-wide association study (GWAS) data and imputation methods in a combined sample of parent/affected child trios from two ASD family collections to explore this hypothesis.

Combining information from 3 anatomic regions in the diagnosis of glaucoma with time-domain optical coherence tomography.

Purpose: To improve the diagnosis of glaucoma by combining time-domain optical coherence tomography (TD-OCT) measurements of the optic disc, circumpapillary retinal nerve fiber layer (RNFL), and macular retinal thickness.

Patients And Methods: Ninety-six age-matched normal and 96 perimetric glaucoma participants were included in this observational, cross-sectional study. Or-logic, support vector machine, relevance vector machine, and linear discrimination function were used to analyze the performances of combined TD-OCT diagnostic variables.

Does optic nerve head size variation affect circumpapillary retinal nerve fiber layer thickness measurement by optical coherence tomography?

Purpose: To determine the relationship between retinal nerve fiber layer (RNFL) thickness, optic disc size, and image magnification.

Methods: The cohort consisted of 196 normal eyes of 101 participants in the Advanced Imaging for Glaucoma Study (AIGS), a multicenter, prospective, longitudinal study to develop advanced imaging technologies for glaucoma diagnosis. Scanning laser tomography was used to measure disc size.

Prediction of serotonin transporter promoter polymorphism genotypes from single nucleotide polymorphism arrays using machine learning methods.

Background: The serotonin transporter gene (SLC6A4) and its promoter (5-HTTLPR) polymorphism have been the focus of a large number of association studies of behavioral traits and psychiatric disorders. However, large-scale genotyping of the polymorphism has been very difficult. We report the development and validation of a 5-HTTLPR genotype prediction model.

Reproducibility of tear meniscus measurement by Fourier-domain optical coherence tomography: a pilot study.

Background And Objective: To study the reproducibility of tear meniscus measurement with high-speed high-resolution Fourier-domain optical coherence tomography (FD-OCT).

Patients And Methods: Twenty normal participants were enrolled in this prospective study. The lower tear meniscus in the right eye of each subject was imaged by vertical scans centered on the inferior cornea and the lower eyelid using an FD-OCT system (RTVue; Optovue, Inc.

Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical coherence tomography.

Purpose: To map ganglion cell complex (GCC) thickness with high-speed Fourier-domain optical coherence tomography (FD-OCT) and compute novel macular parameters for glaucoma diagnosis.

Design: Observational, cross-sectional study.

Participants: One hundred seventy-eight participants in the Advanced Imaging for Glaucoma Study, divided into 3 groups: 65 persons in the normal group, 78 in the perimetric glaucoma group (PG), and 52 in the preperimetric glaucoma group (PPG).

Correlation of Fourier domain optical coherence tomography retinal nerve fiber layer maps with visual fields in nonarteritic ischemic optic neuropathy.

Background And Objective: To correlate peripapillary retinal nerve fiber layer (NFL) loss and visual field defects in nonarteritic ischemic optic neuropathy (NAION).

Patients And Methods: Patients with NAION and control subjects were enrolled in a case-control study. Participants were scanned with a Fourier domain optical coherence tomography (OCT) system.

Combining nerve fiber layer parameters to optimize glaucoma diagnosis with optical coherence tomography.

Purpose: To identify the best combination of Stratus optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness parameters for the detection of glaucoma.

Design: Observational cross-sectional study.

Participants: Eighty-nine age-matched normal and perimetric glaucoma participants enrolled in the Advanced Imaging for Glaucoma Study.

Mapping of macular substructures with optical coherence tomography for glaucoma diagnosis.

Purpose: To use optical coherence tomography (OCT) to identify the specific retinal layers and macular regions damaged in glaucoma.

Design: Observational cross-sectional study.

Participants: One hundred forty-nine participants in the Advanced Imaging for Glaucoma Study, divided into 3 groups: normal (N) perimetric glaucoma (PG), and glaucoma suspect and preperimetric glaucoma (GSPPG) with 44, 73, and 29 persons, respectively.

Weighted variance FBAT: a powerful method for including covariates in FBAT analyses.

The family-based association test (FBAT), an extension of transmission/disequilibrium test, capitalizes on linkage disequilibrium to assess the association of genetic markers and traits in nuclear families. It does not permit a formal inclusion of covariates, although an offset under the FBAT -o option allows for an overall trait-intercept adjustment. The PBAT software provides additional features and permits the inclusion of covariates in the FBAT test statistic, but does not account for the parental genotype information when the traits are adjusted for the covariates.