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Open AccessJournal ArticleDOI

Genomic control for association studies.

Bernie Devlin, +1 more
- 01 Dec 1999 - 
- Vol. 55, Iss: 4, pp 997-1004
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TLDR
The performance of the genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders.
Abstract
A dense set of single nucleotide polymorphisms (SNP) covering the genome and an efficient method to assess SNP genotypes are expected to be available in the near future. An outstanding question is how to use these technologies efficiently to identify genes affecting liability to complex disorders. To achieve this goal, we propose a statistical method that has several optimal properties: It can be used with case control data and yet, like family-based designs, controls for population heterogeneity; it is insensitive to the usual violations of model assumptions, such as cases failing to be strictly independent; and, by using Bayesian outlier methods, it circumvents the need for Bonferroni correction for multiple tests, leading to better performance in many settings while still constraining risk for false positives. The performance of our genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders.

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Journal ArticleDOI

A mixture model approach for the analysis of microarray gene expression data

TL;DR: A sequence of procedures involving finite mixture modeling and bootstrap inference is developed to address issues in studies involving many thousands of genes, including calorically restricted mice.
Journal ArticleDOI

FTO genotype is associated with phenotypic variability of body mass index

Jian Yang, +198 more
- 11 Oct 2012 - 
TL;DR: The authors performed a meta-analysis of genome-wide association studies of phenotypic variation using ∼170,000 samples on height and body mass index (BMI) in human populations.

Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps

Anubha Mahajan, +113 more
Abstract: We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%, 14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.
Journal ArticleDOI

Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension

Sandosh Padmanabhan, +82 more
- 28 Oct 2010 - 
TL;DR: The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
References
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Book

Statistical Decision Theory and Bayesian Analysis

TL;DR: An overview of statistical decision theory, which emphasizes the use and application of the philosophical ideas and mathematical structure of decision theory.
Journal ArticleDOI

The Future of Genetic Studies of Complex Human Diseases

TL;DR: The identification of the genetic basis of complex human diseases such as schizophrenia and diabetes has proven difficult as mentioned in this paper, and Risch and Merikangas proposed that they can best accomplish this goal by combining the power of the human genome project with association studies.
Journal ArticleDOI

An Introduction to Population Genetics Theory

James F. Crow, +1 more
- 01 Sep 1971 - 
TL;DR: An introduction to population genetics theory, An introduction to Population Genetics Theory, Population Genetics theory, Population genetics theory as discussed by the authors, Population genetics, population genetics, and population genetics theories, Population Genetic Theory
Book

An introduction to population genetics theory

TL;DR: An introduction to population genetics theory, An introduction to Population Genetics theory, and more.
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