Genome-wide haplotypic testing in a Finnish cohort identifies a novel association with low-density lipoprotein cholesterol

@article{Zhang2015GenomewideHT,
  title={Genome-wide haplotypic testing in a Finnish cohort identifies a novel association with low-density lipoprotein cholesterol},
  author={Qian S Zhang and Brian L. Browning and Sharon R. Browning},
  journal={European Journal of Human Genetics},
  year={2015},
  volume={23},
  pages={672-677}
}
We performed genome-wide tests for association between haplotype clusters and each of 9 metabolic traits in a cohort of 5402 Northern Finnish individuals genotyped for 330 000 single-nucleotide polymorphisms. The metabolic traits were body mass index, C-reactive protein, diastolic blood pressure, glucose, high-density lipoprotein (HDL), insulin, low-density lipoprotein (LDL), systolic blood pressure, and triglycerides. Haplotype clusters were determined using Beagle. There were LDL-associated… 

Multi-strategy genome-wide association studies identify the DCAF16-NCAPG region as a susceptibility locus for average daily gain in cattle

The results from the multi-strategy GWASs revealed the DCAF16-NCAPG region to be a susceptibility locus for ADG in cattle.

Haplotype sharing provides insights into fine-scale population history and disease in Finland

It is found that there was more continuous gene flow as Finns migrated from southwest to northeast between the early- and late-settlement regions than was dichotomously described previously, and haplotype sharing is locally enriched by an order of magnitude.

Redefining replication in multi-ancestry genome-wide association

It is argued that enrichment analyses which aggregate SNP-level association statistics at multiple genomic scales—to genes 31 and pathways—have been overlooked and can generate biologically interpretable hypotheses regarding the genetic basis of complex trait architecture.

Interaction Landscape of Inherited Polymorphisms with Somatic Events in Cancer.

Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms

Rapidly Registering Identity-by-Descent Across Ancestral Recombination Graphs

This work uses computationally efficient approaches to extract ground-truth IBD segments from a sequence of genealogies, or equivalently, an ancestral recombination graph, using a two-step scheme.

An Evaluation of the PrediXcan Method for the Identification of Lipid Associated Genes

A comparison of p values for matched genes between PrediXcan and MLR models showed weak correlations but strong evidence for LDL and HDL associations with genes at locus 1p13.3 and 16q13, respectively.

A minor allele of the haplotype located in the 19q13 loci is associated with a decreased risk of hyper-LDL-cholesterolemia, and a balanced diet and high protein intake can reduce the risk

The minor allele of haplotype located in 19q13 loci protected against hyper-LDL-cholesterolemia, especially with BD and high protein intake, and also had a negative association with myocardial infarction events.

Statistical Genetic Methods and Applications for Population Structure

References

SHOWING 1-10 OF 20 REFERENCES

Genome-wide association analysis of metabolic traits in a birth cohort from a founder population

The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.

Biological, Clinical, and Population Relevance of 95 Loci for Blood Lipids

The results identify several novel loci associated with plasma lipids that are also associated with CAD and provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

Potential etiologic and functional implications of genome-wide association loci for human diseases and traits

An online catalog of SNP-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated SNPs (TASs) is developed, well-suited to guide future investigations of the role of common variants in complex disease etiology.

Joint analysis of tightly linked SNPs in screening step of genome-wide association studies leads to increased power

It is shown through a power simulation study that a simultaneous analysis of tightly linked SNPs in the initial GWAS analysis step would lead to increased power, when compared with that in single-marker analysis.

Performance of Genotype Imputation for Rare Variants Identified in Exons and Flanking Regions of Genes

Routine use of genotype imputation is suggested for extending the assessment of common variants identified in humans via targeted exon resequencing into additional samples with GWAS data, but imputation of very rare variants (MAF< = 0.005) will require reference panels with thousands of subjects.

A second generation human haplotype map of over 3.1 million SNPs

The Phase II HapMap is described, which characterizes over 3.1 million human single nucleotide polymorphisms genotyped in 270 individuals from four geographically diverse populations and includes 25–35% of common SNP variation in the populations surveyed, and increased differentiation at non-synonymous, compared to synonymous, SNPs is demonstrated.

Efficient multilocus association testing for whole genome association studies using localized haplotype clustering

A combined single‐marker and haplotypic strategy is proposed, in which both single‐ Marker and Haplotypic tests are applied, with the minimum P‐value adjusted for multiple testing by permutation which results in a test that is powerful for detecting both low‐and high‐frequency disease‐susceptibility variants.

Haplotypic analysis of Wellcome Trust Case Control Consortium data

Localized haplotype cluster analysis had better success detecting disease associated variants than a previous single-marker analysis of imputed HapMap SNPs.

Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering.

This work presents a new method and software for inference of haplotypes phase and missing data that can accurately phase data from whole-genome association studies, and presents the first comparison of haplotype-inference methods for real and simulated data sets with thousands of genotyped individuals.

PLINK: a tool set for whole-genome association and population-based linkage analyses.

This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.