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PreprintCited by 366Genetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and AnimalsForensic and Genetic Research

The Relative Power of Family-Based and Case-Control Designs for Linkage Disequilibrium Studies of Complex Human Diseases I. DNA Pooling

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Risch, Neil, Teng, Jun·1998·Genome Research
DOI 10.1101/gr.8.12.1273
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Abstract

We consider statistics for analyzing a variety of family-based and nonfamily-based designs for detecting linkage disequilibrium of a marker with a disease susceptibility locus. These designs include sibships with parents, sibships without parents, and use of unrelated controls. We also provide formulas for and evaluate the relative power of different study designs using these statistics. In this first paper in the series, we derive statistical tests based on data derived from DNA pooling experiments and describe their characteristics. Although designs based on affected and unaffected sibs without parents are usually robust to population stratification, they suffer a loss of power compared with designs using parents or unrelateds as controls. Although increasing the number of unaffected sibs improves power, the increase is generally not substantial. Designs including sibships with multiple affected sibs are typically the most powerful, with any of these control groups, when the disease allele frequency is low. When the allele frequency is high, however, designs with unaffected sibs as controls do not retain this advantage. In designs with parents, having an affected parent has little impact on the power, except for rare dominant alleles, where the power is increased compared with families with no affected parents. Finally, we also demonstrate that for sibships with parents, only the parents require individual genotyping to derive the TDT statistic, whereas all the offspring can be pooled. This can potentially lead to considerable savings in genotyping, especially for multiplex sibships. The formulas and tables we derive should provide some guidance to investigators designing nuclear family-based linkage disequilibrium studies for complex diseases.

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  • The association test was repeated correcting for the relatedness of the patients by extending a variance-adjustment procedure to apply to general familial relationships.

    “As the patient cohort was recruited as families for a linkage analysis, we also repeated the test for association, correcting for the relatedness of the patients by extending a variance-adjustment procedure described previously [24] for sib-ships to apply to general familial relationships.”

    From CFH Y402H confers similar risk of soft drusen and both forms of advanced AMD (2005) · cites this paper as [24]

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Authors
Risch, N., & Teng, J.
Affiliations
Stanford Medicine (US)
ORCID
Risch, Neil
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
1998-12-01
Volume
8
Issue
12
Pages
1273-1288
ISSN
  • 1088-9051 (ISSN-L)
  • 1549-5469
DOI
10.1101/gr.8.12.1273
OpenAlex
W2096051150
Cited by
366
References
25
Citations by year
2024: 1 · 2021: 1 · 2019: 2 · 2017: 2 · 2016: 3 · 2015: 7 · 2014: 4 · 2013: 8 · 2012: 7
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hg000348-09)
  • National Human Genome Research Institute (HG00348)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
Keywords
linkage disequilibrium, family-based association study, case-control study, DNA pooling, affected sibships, statistical power, population stratification, complex diseases, disease susceptibility loci
MeSH terms
DNA, Humans, Models, Genetic, Pedigree, Research Design, Linkage Disequilibrium, Case-Control Studies, Genetic Diseases, Inborn

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