5
Methods for Association Studies
Rebecca E. Graff, Caroline G. Tai, Linda Kachuri, and John S. Witte
Abstract
Association studies are a key approach to evaluating the relationship between
genetic factors and phenotypes or traits. This chapter presents general methods
for genetic association studies in unrelated humans. Topics covered include
types of association studies, study design considerations, measurement of genetic
information, and analytical techniques. This material provides readers with
background for interpreting results from association studies and for undertaking
their own studies.
5.1
Introduction
Since the first sequences of base pairs were published in the late 1960s and early
1970s (Gilbert and Maxam 1973; Wu and Kaiser 1968; Wu and Taylor 1971),
our ability to investigate the human genome has advanced immensely. Genetic
epidemiology largely aims to identify genetic factors that are associated with a
particular phenotype or disease state. To evaluate these relationships, one essential
approach used by researchers is the genetic association study. These studies relate
germline genetic variants—or other sources of genetic variation—to some measure
of phenotype, disease status, progression, and/or mortality.
Before association studies became pervasive in the journey toward deciphering
the genetic basis of complex disease, linkage analysis was a common method
for detecting genes with a major effect on phenotype (Claussnitzer et al. 2020).
In the 1980s and early 1990s, many researchers undertook genetic studies that
R. E. Graff () · C. G. Tai · L. Kachuri · J. S. Witte
Department of Epidemiology and Biostatistics, University of California, San Francisco, San
Francisco, CA, USA
e-mail: Rebecca.Graff@ucsf.edu
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2021
K. E. Lohmueller, R. Nielsen (eds.), Human Population Genomics,
https://doi.org/10.1007/978-3-030-61646-5_5
89
Methods for Association Studies
Rebecca E. Graff, Caroline G. Tai, Linda Kachuri, and John S. Witte
Abstract
Association studies are a key approach to evaluating the relationship between
genetic factors and phenotypes or traits. This chapter presents general methods
for genetic association studies in unrelated humans. Topics covered include
types of association studies, study design considerations, measurement of genetic
information, and analytical techniques. This material provides readers with
background for interpreting results from association studies and for undertaking
their own studies.
5.1
Introduction
Since the first sequences of base pairs were published in the late 1960s and early
1970s (Gilbert and Maxam 1973; Wu and Kaiser 1968; Wu and Taylor 1971),
our ability to investigate the human genome has advanced immensely. Genetic
epidemiology largely aims to identify genetic factors that are associated with a
particular phenotype or disease state. To evaluate these relationships, one essential
approach used by researchers is the genetic association study. These studies relate
germline genetic variants—or other sources of genetic variation—to some measure
of phenotype, disease status, progression, and/or mortality.
Before association studies became pervasive in the journey toward deciphering
the genetic basis of complex disease, linkage analysis was a common method
for detecting genes with a major effect on phenotype (Claussnitzer et al. 2020).
In the 1980s and early 1990s, many researchers undertook genetic studies that
R. E. Graff () · C. G. Tai · L. Kachuri · J. S. Witte
Department of Epidemiology and Biostatistics, University of California, San Francisco, San
Francisco, CA, USA
e-mail: Rebecca.Graff@ucsf.edu
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2021
K. E. Lohmueller, R. Nielsen (eds.), Human Population Genomics,
https://doi.org/10.1007/978-3-030-61646-5_5
89