Computational Systems Biology Methods and Protocols.7z

Chapter 6

An Overview of Genome-Wide Association Studies

Michelle Chang, Lin He, and Lei Cai

Abstract

Genome-wide association study (GWAS) is a powerful study design to identify genetic variants of a trait
and, in particular, detect the association between common single-nucleotide polymorphisms (SNPs) and
common human diseases such as heart disease, inflammatory bowel disease, type 2 diabetes, and psychiatric
disorders. The standard strategy of population-based case-control studies for GWAS is illustrated in this
chapter. We provide an overview of the concepts underlying GWAS, as well as provide guidelines for
statistical methods performed in GWAS.

Key wordsGenome-wide association studies, SNPs, Linkage disequilibrium, Case-control, Two-

stage analysis, Genotyping, Common disease common variant hypothesis

1 Introduction

In the early age, linkage analysis and gene mapping had been

successfully used for detecting gene variants affecting Mendelian

traits (i.e., single-gene disorders, such as cystic fibrosis). However,

for complex diseases such as heart disease and inflammatory bowel

disease, genetic association studies are more efficient to identify

common and penetrant variants implicated in common disease

than the classical approaches, such as linkage analysis or candidate

gene (CG), due to the idea of common diseases related to multiple

susceptibility variants. This is also termed “common disease-

common variant hypothesis.” This hypothesis states that common

diseases are likely influenced by genetic variation that is also com-

mon in the population. Over the last 5 years, it has been tested for a

variety of common disorders, and while some of the heritability for

these conditions are not yet explained, common alleles certainly

play a role in susceptibility, though it should not be assumed that

the entire genetic component of any common disease is due to

common alleles only. The National Human Genome Research

Institute GWAS Catalog lists over 3600 SNPs identified for com-

mon diseases or traits, and in general, common diseases have

Tao Huang (ed.),Computational Systems Biology: Methods and Protocols, Methods in Molecular Biology, vol. 1754,
https://doi.org/10.1007/978-1-4939-7717-8_6,©Springer Science+Business Media, LLC, part of Springer Nature 2018

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