Using the noninformative families in family-based association tests: a powerful new testing strategy - PubMed (original) (raw)
Using the noninformative families in family-based association tests: a powerful new testing strategy
Christoph Lange et al. Am J Hum Genet. 2003 Oct.
Abstract
For genetic association studies with multiple phenotypes, we propose a new strategy for multiple testing with family-based association tests (FBATs). The strategy increases the power by both using all available family data and reducing the number of hypotheses tested while being robust against population admixture and stratification. By use of conditional power calculations, the approach screens all possible null hypotheses without biasing the nominal significance level, and it identifies the subset of phenotypes that has optimal power when tested for association by either univariate or multivariate FBATs. An application of our strategy to an asthma study shows the practical relevance of the proposed methodology. In simulation studies, we compare our testing strategy with standard methodology for family studies. Furthermore, the proposed principle of using all data without biasing the nominal significance in an analysis prior to the computation of the test statistic has broad and powerful applications in many areas of family-based association studies.
Figures
Figure 1
Histogram of environmental correlations
Similar articles
- Screening and replication using the same data set: testing strategies for family-based studies in which all probands are affected.
Murphy A, Weiss ST, Lange C. Murphy A, et al. PLoS Genet. 2008 Sep 19;4(9):e1000197. doi: 10.1371/journal.pgen.1000197. PLoS Genet. 2008. PMID: 18802462 Free PMC article. - A new powerful non-parametric two-stage approach for testing multiple phenotypes in family-based association studies.
Lange C, Lyon H, DeMeo D, Raby B, Silverman EK, Weiss ST. Lange C, et al. Hum Hered. 2003;56(1-3):10-7. doi: 10.1159/000073728. Hum Hered. 2003. PMID: 14614234 - On the analysis of copy-number variations in genome-wide association studies: a translation of the family-based association test.
Ionita-Laza I, Perry GH, Raby BA, Klanderman B, Lee C, Laird NM, Weiss ST, Lange C. Ionita-Laza I, et al. Genet Epidemiol. 2008 Apr;32(3):273-84. doi: 10.1002/gepi.20302. Genet Epidemiol. 2008. PMID: 18228561 - A multivariate family-based association test using generalized estimating equations: FBAT-GEE.
Lange C, Silverman EK, Xu X, Weiss ST, Laird NM. Lange C, et al. Biostatistics. 2003 Apr;4(2):195-206. doi: 10.1093/biostatistics/4.2.195. Biostatistics. 2003. PMID: 12925516
Cited by
- Incorporating parental information into family-based association tests.
Yu Z, Gillen D, Li CF, Demetriou M. Yu Z, et al. Biostatistics. 2013 Jul;14(3):556-72. doi: 10.1093/biostatistics/kxs048. Epub 2012 Dec 23. Biostatistics. 2013. PMID: 23266418 Free PMC article. - Comparison of linkage and association strategies for quantitative traits using the COGA dataset.
McQueen MB, Murphy A, Kraft P, Su J, Lazarus R, Laird NM, Lange C, Van Steen K. McQueen MB, et al. BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S96. doi: 10.1186/1471-2156-6-S1-S96. BMC Genet. 2005. PMID: 16451712 Free PMC article. - A three-stage approach for genome-wide association studies with family data for quantitative traits.
Chen MH, Larson MG, Hsu YH, Peloso GM, Guo CY, Fox CS, Atwood LD, Yang Q. Chen MH, et al. BMC Genet. 2010 May 14;11:40. doi: 10.1186/1471-2156-11-40. BMC Genet. 2010. PMID: 20470424 Free PMC article. - Differential association between the norepinephrine transporter gene and ADHD: role of sex and subtype.
Sengupta SM, Grizenko N, Thakur GA, Bellingham J, DeGuzman R, Robinson S, TerStepanian M, Poloskia A, Shaheen SM, Fortier ME, Choudhry Z, Joober R. Sengupta SM, et al. J Psychiatry Neurosci. 2012 Feb;37(2):129-37. doi: 10.1503/jpn.110073. J Psychiatry Neurosci. 2012. PMID: 22297068 Free PMC article. - Family-based association analysis: a fast and efficient method of multivariate association analysis with multiple variants.
Won S, Kim W, Lee S, Lee Y, Sung J, Park T. Won S, et al. BMC Bioinformatics. 2015 Feb 15;16:46. doi: 10.1186/s12859-015-0484-5. BMC Bioinformatics. 2015. PMID: 25887481 Free PMC article.
References
Electronic-Database Information
- PBAT Web Page, http://www.biosun1.harvard.edu/~clange/pbat.htm (for PBAT software)
References
- DeMeo DL, Lange C, Silverman EK, Senter JM, Drazen JM, Barth MJ, Laird NM, Weiss ST (2002) Univariate and multivariate family based analysis of the arg130gln polymorphism of the IL13 gene in the childhood asthma management program. Genet Epidemiol 23:335–348 - PubMed
- Falconer DS, Mackay TFC (1997) Introduction to quantitative genetics. Longman, New York
- Childhood Asthma Management Program Research Group (1999) The childhood asthma management program (CAMP): design, rationale, and methods. Control Clin Trials 20:91–120 - PubMed
- Laird NM, Horvath S, Xu X (2000) Implementing a unified approach to family based tests of association. Genet Epidemiol Suppl 19:S36–S42 - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- N01-NR-01646/NR/NINR NIH HHS/United States
- P01 HL67664/HL/NHLBI NIH HHS/United States
- T32HL67427/HL/NHLBI NIH HHS/United States
- N01-NR-01651/NR/NINR NIH HHS/United States
- R01 NL66386/PHS HHS/United States
- N01 HLC6795/HL/NHLBI NIH HHS/United States
- HL66795/HL/NHLBI NIH HHS/United States
- N01-NR-01647/NR/NINR NIH HHS/United States
- T32 HL07427/HL/NHLBI NIH HHS/United States
- R01 HL66386/HL/NHLBI NIH HHS/United States
- N01-NR-01650/NR/NINR NIH HHS/United States
- N01-NR-01644/NR/NINR NIH HHS/United States
- N01-NR-01649/NR/NINR NIH HHS/United States
- N01-NR-01652/NR/NINR NIH HHS/United States
- N01-NR-01648/NR/NINR NIH HHS/United States
- N01-NR-01645/NR/NINR NIH HHS/United States
- N01 HR16049/HR/NHLBI NIH HHS/United States
- P01 HL067664/HL/NHLBI NIH HHS/United States
- T32 HL007427/HL/NHLBI NIH HHS/United States
- N01HR16049/HR/NHLBI NIH HHS/United States
- U01 HL066795/HL/NHLBI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Medical