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1.  Kernel score statistic for dependent data 
BMC Proceedings  2014;8(Suppl 1):S41.
The kernel score statistic is a global covariance component test over a set of genetic markers. It provides a flexible modeling framework and does not collapse marker information. We generalize the kernel score statistic to allow for familial dependencies and to adjust for random confounder effects. With this extension, we adjust our analysis of real and simulated baseline systolic blood pressure for polygenic familial background. We find that the kernel score test gains appreciably in power through the use of sequencing compared to tag-single-nucleotide polymorphisms for very rare single nucleotide polymorphisms with <1% minor allele frequency.
doi:10.1186/1753-6561-8-S1-S41
PMCID: PMC4143755  PMID: 25519324
2.  Genetic Analysis Workshop 18: Methods and strategies for analyzing human sequence and phenotype data in members of extended pedigrees 
BMC Proceedings  2014;8(Suppl 1):S1.
Genetic Analysis Workshop 18 provided a platform for developing and evaluating statistical methods to analyze whole-genome sequence data from a pedigree-based sample. In this article we present an overview of the data sets and the contributions that analyzed these data. The family data, donated by the Type 2 Diabetes Genetic Exploration by Next-Generation Sequencing in Ethnic Samples Consortium, included sequence-level genotypes based on sequencing and imputation, genome-wide association genotypes from prior genotyping arrays, and phenotypes from longitudinal assessments. The contributions from individual research groups were extensively discussed before, during, and after the workshop in theme-based discussion groups before being submitted for publication.
doi:10.1186/1753-6561-8-S1-S1
PMCID: PMC4143625  PMID: 25519310
3.  Identifying rare variants from exome scans: the GAW17 experience 
BMC Proceedings  2011;5(Suppl 9):S1.
Genetic Analysis Workshop 17 (GAW17) provided a platform for evaluating existing statistical genetic methods and for developing novel methods to analyze rare variants that modulate complex traits. In this article, we present an overview of the 1000 Genomes Project exome data and simulated phenotype data that were distributed to GAW17 participants for analyses, the different issues addressed by the participants, and the process of preparation of manuscripts resulting from the discussions during the workshop.
doi:10.1186/1753-6561-5-S9-S1
PMCID: PMC3287821  PMID: 22373325
4.  Integration of a priori gene set information into genome-wide association studies 
BMC Proceedings  2009;3(Suppl 7):S95.
In genome-wide association studies (GWAS) genetic markers are often ranked to select genes for further pursuit. Especially for moderately associated and interrelated genes, information on genes and pathways may improve the selection. We applied and combined two main approaches for data integration to a GWAS for rheumatoid arthritis, gene set enrichment analysis (GSEA) and hierarchical Bayes prioritization (HBP). Many associated genes are located in the HLA region on 6p21. However, the ranking lists of genes and gene sets differ considerably depending on the chosen approach: HBP changes the ranking only slightly and primarily contains HLA genes in the top 100 gene lists. GSEA includes also many non-HLA genes.
doi:10.1186/1753-6561-3-S7-S95
PMCID: PMC2795999  PMID: 20018092
5.  Tests for candidate-gene interaction for longitudinal quantitative traits measured in a large cohort 
BMC Proceedings  2009;3(Suppl 7):S80.
For the Framingham Heart Study (FHS) and simulated FHS (FHSsim) data, we tested for gene-gene interaction in quantitative traits employing a longitudinal nonparametric association test (LNPT) and, for comparison, a survival analysis. We report results for the Offspring Cohort by LNPT analysis and on all longitudinal cohorts by survival analysis with cohort effect adjustment. We verified that type I errors were not inflated. We compared the power of both methods to detect in FHSsim data two sets of gene pairs that interact for the trait coronary artery calcification. In FHS, we tested eight gene pairs from a list of candidate genes for interaction effects on body mass index. Both methods found evidence for pairwise non-additive effects of mutations in the genes FTO, PON1, and PFKP on body mass index.
PMCID: PMC2795983  PMID: 20018076
8.  Case-control studies with affected sibships 
BMC Proceedings  2007;1(Suppl 1):S29.
Related cases may be included in case-control association studies if correlations between related individuals due to identity-by-descent (IBD) sharing are taken into account. We derived a framework to test for association in a case-control design including affected sibships and unrelated controls. First, a corrected variance for the allele frequency difference between cases and controls was directly calculated or estimated in two ways on the basis of the fixation index FST and the inbreeding coefficient. Then the correlation-corrected association test including controls and affected sibs was carried out. We applied the three strategies to 20 candidate genes on the Genetic Analysis Workshop 15 rheumatoid arthritis data and to 9187 single-nucleotide polymorphisms of replicate one of the Genetic Analysis Workshop 15 simulated data with knowledge of the "answers". The three strategies used to correct for correlation give only minor differences in the variance estimates and yield an almost correct type I error rate for the association tests. Thus, all strategies considered to correct the variance performed quite well.
PMCID: PMC2367527  PMID: 18466526

Results 1-8 (8)