Accurate power approximations for χ<sup>2</sup>‐tests in case‐control association studies of complex disease genes

Jackson, Michael R.; Génin, Emmanuelle; Knapp, Michael; Escary, Jean-Louis

doi:10.1046/j.1469-1809.2002.00120.x

Cited by 25 publications

(17 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The power (for alpha = 0.05/17 = 0.003) of the present study was calculated for a marker with a minor allele frequency (MAF) of 0.20 and a dose-dependent genetic effect in accordance with Jackson et al [17]. A dose-dependent genetic effect has been observed for all proven NSCL/P loci to date [7,8].…”

Section: Discussionmentioning

confidence: 95%

SUMO1 as a candidate gene for non-syndromic cleft lip with or without cleft palate: No evidence for the involvement of common or rare variants in Central European patients

Assis

Nowak

Ludwig

et al. 2011

International Journal of Pediatric Otorhinolaryngology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 95%

SUMO1 as a candidate gene for non-syndromic cleft lip with or without cleft palate: No evidence for the involvement of common or rare variants in Central European patients

Assis

Nowak

Ludwig

et al. 2011

International Journal of Pediatric Otorhinolaryngology

View full text Add to dashboard Cite

“…Briefly, a number of approximate power functions for independence w 2 tests and trend tests have been proposed in the literature [Bukszar and van den Oord, 2006;Chapman and Nam, 1968;Jackson et al, 2002;Slager and Schaid, 2001;Thomas, 1996]. Power comparison in principle can be done by plugging alternative parameters into approximate power functions, but most of them require that each expected cell count is greater than 5, which might not be true in reality.…”

Section: Methods For Power Calculationmentioning

confidence: 99%

What's the best statistic for a simple test of genetic association in a case‐control study?

Kuo

Feingold

2009

Genetic Epidemiology

View full text Add to dashboard Cite

Genome-wide genetic association studies typically start with univariate statistical tests of each marker. In principle, this single-SNP scanning is statistically straightforward--the testing is done with standard methods (e.g. chi(2) tests, regression) that have been well studied for decades. However, a number of different tests and testing procedures can be used. In a case-control study, one can use a 1 df allele-based test, a 1 or 2 df genotype-based test, or a compound procedure that combines two or more of these statistics. Additionally, most of the tests can be performed with or without covariates included in the model. While there are a number of statistical papers that make power comparisons among subsets of these methods, none has comprehensively tackled the question of which of the methods in common use is best suited to univariate scanning in a genome-wide association study. In this paper, we consider a wide variety of realistic test procedures, and first compare the power of the different procedures to detect a single locus under different genetic models. We then address the question of whether or when it is a good idea to include covariates in the analysis. We conclude that the most commonly used approach to handle covariates--modeling covariate main effects but not interactions--is almost never a good idea. Finally, we consider the performance of the statistics in a genome scan context.

show abstract

“…We genotyped 116 Central European individuals with nonsyndromic submucous palatal clefts using PCR followed by direct genotyping, but we did not find a significant association when compared to the 267 Central European control subjects (p ¼ 0.94). Given the statistical power to detect an association of the effect size found in the nsCPO sample (0.87, calculated according to Jackson et al 25 ), we conclude that, although rare GRHL3 variants can lead to a submucous palatal cleft, rs41268753 does not significantly contribute to this subphenotype of CPO.…”

mentioning

confidence: 90%

Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate

Mangold

Böhmer

Ishorst

et al. 2016

The American Journal of Human Genetics

View full text Add to dashboard Cite

Nonsyndromic cleft lip with/without cleft palate (nsCL/P) and nonsyndromic cleft palate only (nsCPO) are the most frequent subphenotypes of orofacial clefts. A common syndromic form of orofacial clefting is Van der Woude syndrome (VWS) where individuals have CL/P or CPO, often but not always associated with lower lip pits. Recently, ∼5% of VWS-affected individuals were identified with mutations in the grainy head-like 3 gene (GRHL3). To investigate GRHL3 in nonsyndromic clefting, we sequenced its coding region in 576 Europeans with nsCL/P and 96 with nsCPO. Most strikingly, nsCPO-affected individuals had a higher minor allele frequency for rs41268753 (0.099) than control subjects (0.049; p = 1.24 × 10(-2)). This association was replicated in nsCPO/control cohorts from Latvia, Yemen, and the UK (pcombined = 2.63 × 10(-5); ORallelic = 2.46 [95% CI 1.6-3.7]) and reached genome-wide significance in combination with imputed data from a GWAS in nsCPO triads (p = 2.73 × 10(-9)). Notably, rs41268753 is not associated with nsCL/P (p = 0.45). rs41268753 encodes the highly conserved p.Thr454Met (c.1361C>T) (GERP = 5.3), which prediction programs denote as deleterious, has a CADD score of 29.6, and increases protein binding capacity in silico. Sequencing also revealed four novel truncating GRHL3 mutations including two that were de novo in four families, where all nine individuals harboring mutations had nsCPO. This is important for genetic counseling: given that VWS is rare compared to nsCPO, our data suggest that dominant GRHL3 mutations are more likely to cause nonsyndromic than syndromic CPO. Thus, with rare dominant mutations and a common risk variant in the coding region, we have identified an important contribution for GRHL3 in nsCPO.

show abstract

Accurate power approximations for χ²‐tests in case‐control association studies of complex disease genes

Cited by 25 publications

References 8 publications

SUMO1 as a candidate gene for non-syndromic cleft lip with or without cleft palate: No evidence for the involvement of common or rare variants in Central European patients

SUMO1 as a candidate gene for non-syndromic cleft lip with or without cleft palate: No evidence for the involvement of common or rare variants in Central European patients

What's the best statistic for a simple test of genetic association in a case‐control study?

Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate

Contact Info

Product

Resources

About

Accurate power approximations for χ2‐tests in case‐control association studies of complex disease genes

Cited by 25 publications

References 8 publications

SUMO1 as a candidate gene for non-syndromic cleft lip with or without cleft palate: No evidence for the involvement of common or rare variants in Central European patients

SUMO1 as a candidate gene for non-syndromic cleft lip with or without cleft palate: No evidence for the involvement of common or rare variants in Central European patients

What's the best statistic for a simple test of genetic association in a case‐control study?

Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate

Contact Info

Product

Resources

About

Accurate power approximations for χ²‐tests in case‐control association studies of complex disease genes