- Genotyped cases and controls data from the Wellcome Trust
Case Control Consortium (WTCCC):
https://www.wtccc.org.uk/. - Genotyped cases and controls data from UK Biobank:
http://www.ukbiobank.ac.uk/.
3 Methods
The goal of GWAS is to understand the variation in complex traits
and diseases by relating genotypes of SNPs to observed pheno-
types. To do this, it is necessary to detect which markers are
associated with variation in the traits. In this section we aim to
provide an overview of the methods available for case-control
designs in GWAS.3.1 Determine the
Disease of Interest
for GWAS
Defining the disease or phenotype of interest as accurately and
specifically as possible is the first step in a case-control design.
Without specific case definitions, both the genetic and the environ-
mental heterogeneity will increase in underlying causal factors,
while the power of detection of an effect drastically decreases. In
this part, we introduce the fundamental thoughts before you per-
form experimental design of GWAS with sufficient power to
robustly detect genomic effects.- Define a consensus case definition of the disease of interest
from relevant organizations, such as the World Health Organi-
zation or recognized disease-specified associations to standard-
ize phenotype [9](seeNote 2). - Determine the heritability of the disease with available evidence
from familial studies (seeNote 3). - Consider whether the etiology of the disease includes one or
more common underlying polymorphisms (allele fre-
quency>0.01) to ensure the population-based study is an
appropriate design for the study.
3.2 Collect Study
Samples and
Genotyping
Two main companies have provided a number of fixed content
panels available for genotyping arrays or chips with set SNPs that
are being evaluated on them. The approaches used to select
the SNPs for these panels, including random SNPs, selected haplo-
type tag SNPs, and the nucleotides chosen to be on these panels
but are actually copy number variations which cause the signal
differs.
Ideally, further phenotypic information should be available for
such a panel so as to exclude known cases and to enable matching of
controls to cases on the adjustment in analysis.An Overview of Genome-Wide Association Studies 101