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Cited by 15Genetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and AnimalsGenetic diversity and population structure

Ascertainment through family history of disease often decreases the power of family-based association studies

Ferreira, Manuel A. R., Sham, Pak, Daly, Mark J., Purcell, Shaun·2007·Behavior Genetics
DOI 10.1007/s10519-007-9149-0
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Abstract

Selection of cases with additional affected relatives has been shown to increase the power of the case-control association design. We investigated whether this strategy can also improve the power of family-based association studies that use the transmission disequilibrium test (TDT), while accounting for the effects of residual polygenic and environmental factors on disease liability. Ascertainment of parent-offspring trios conditional on the proband having affected first-degree relatives almost always reduced the power of the TDT. For many disease models, this reduction was quite considerable. In contrast, for the same sample size, designs that analyzed more than one affected offspring per family often improved power when compared to the standard parent-offspring trio design. Together, our results suggest that (1) residual polygenic and environmental influences should be considered when estimating the power of the TDT for studies that ascertain families with multiple affected relatives; (2) if trios are selected conditional on having additional affected offspring, then it is important to genotype and include in the analysis the additional siblings; (3) the ascertainment strategy should be considered when interpreting results from TDT analyses. Our analytic approach to estimate the asymptotic power of the TDT is implemented online at http://pngu.mgh.harvard.edu/ ~purcell/gpc/.

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Crossref · 10.1007/s10519-007-9149-0

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  • An excess of multiplex families relative to population frequencies could substantially diminish the estimated Vm.

    “Various factors could skew this distribution and thus bias downwards the estimated Vm, a notable one being an excess of multiplex families relative to population frequencies (35,36).”

    From Individual common variants exert weak effects on the risk for autism spectrum disorders (2012) · cites this paper as [36]

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Authors
Ferreira, M. A. R., Sham, P., Daly, M. J., & Purcell, S.
Affiliations
  • Harvard University (US)
  • King's College London (GB)
  • Broad Institute (US)
Corresponding author
Ferreira, Manuel A. R.
ORCID
Venue
Behavior Genetics
Publisher
Springer Science and Business Media LLC
Published
2007-03-20
Volume
37
Issue
4
Pages
631-636
ISSN
  • 0001-8244 (ISSN-L)
  • 1573-3297
DOI
10.1007/s10519-007-9149-0
OpenAlex
W2135678173
Cited by
15
References
14
Citations by year
2021: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2013: 1 · 2012: 3
FWCI
0.89
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Behavior Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
Funders
  • Mesothelioma Applied Research Foundation
  • National Health and Medical Research Council
  • National Medical Research Council
  • National Eye Institute (EY12562, R01EY012562)
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 › Genetic diversity and population structure
Keywords
family-based association study, transmission disequilibrium test, case ascertainment, family history of disease, power analysis, parent-offspring trios
MeSH terms
Adult, Child, Disease, Female, Humans, Male, Medical History Taking, Models, Genetic, Nuclear Family, Pedigree, Linkage Disequilibrium, Prevalence

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