One-stage design is empirically more powerful than two-stage design for family-based genome-wide association studies
Finding a genetic marker associated with a trait is a classic problem in human genetics. Recently, two-stage approaches have gained popularity in marker-trait association studies, in part because researchers hope to reduce the multiple testing problem by testing fewer markers in the final stage. We compared one two-stage family-based approach to an analogous single-stage method, calculating the empirical type I error rates and power for both methods using fully simulated data sets modeled on nuclear families with rheumatoid arthritis, and data sets of real single-nucleotide polymorphism genotypes from Centre d'Etude du Polymorphisme Humain pedigrees with simulated traits. In these analyses performed in the absence of population stratification, the single-stage method was consistently more powerful than the two-stage method for a given type I error rate. To explore the sources of this difference, we performed a case study comparing the individual steps of two-stage designs, the two-stage design itself, and the analogous one-stage design.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2007 |
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| Erschienen: |
2007 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1 Suppl 1 |
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| Enthalten in: |
BMC proceedings - 1 Suppl 1(2007) vom: 28., Seite S137 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rohlfs, Rori V [VerfasserIn] |
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| Themen: |
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| Anmerkungen: |
Date Completed 15.12.2009 Date Revised 28.10.2021 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| Förderinstitution / Projekttitel: |
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NLM179440799 |
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| 520 | |a Finding a genetic marker associated with a trait is a classic problem in human genetics. Recently, two-stage approaches have gained popularity in marker-trait association studies, in part because researchers hope to reduce the multiple testing problem by testing fewer markers in the final stage. We compared one two-stage family-based approach to an analogous single-stage method, calculating the empirical type I error rates and power for both methods using fully simulated data sets modeled on nuclear families with rheumatoid arthritis, and data sets of real single-nucleotide polymorphism genotypes from Centre d'Etude du Polymorphisme Humain pedigrees with simulated traits. In these analyses performed in the absence of population stratification, the single-stage method was consistently more powerful than the two-stage method for a given type I error rate. To explore the sources of this difference, we performed a case study comparing the individual steps of two-stage designs, the two-stage design itself, and the analogous one-stage design | ||
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| 700 | 1 | |a Corey, Mary |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Amy D |e verfasserin |4 aut | |
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