Adaptive linear step-up procedures that control the false discovery rate

Benjamini, Yoav; Krieger, Abba M.; Yekutieli, Daniel

doi:10.1093/biomet/93.3.491

Cited by 2,648 publications

(2,220 citation statements)

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“…dence intervals were calculated to determine pair-wise differences between genotypes while controlling for false discovery rate (FDR) (39). Distance traveled and time spent walking were significantly higher in df/+ relative to other groups, and the time spent lingering was significantly higher in df/+ relative to dp/+ mice.…”

Section: Resultsmentioning

confidence: 99%

Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism

Horev

Ellegood²,

Lerch³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Recurrent copy number variations (CNVs) of human 16p11.2 have been associated with a variety of developmental/neurocognitive syndromes. In particular, deletion of 16p11.2 is found in patients with autism, developmental delay, and obesity. Patients with deletions or duplications have a wide range of clinical features, and siblings carrying the same deletion often have diverse symptoms. To study the consequence of 16p11.2 CNVs in a systematic manner, we used chromosome engineering to generate mice harboring deletion of the chromosomal region corresponding to 16p11.2, as well as mice harboring the reciprocal duplication. These 16p11.2 CNV models have dosage-dependent changes in gene expression, viability, brain architecture, and behavior. For each phenotype, the consequence of the deletion is more severe than that of the duplication. Of particular note is that half of the 16p11.2 deletion mice die postnatally; those that survive to adulthood are healthy and fertile, but have alterations in the hypothalamus and exhibit a "behavior trap" phenotype-a specific behavior characteristic of rodents with lateral hypothalamic and nigrostriatal lesions. These findings indicate that 16p11.2 CNVs cause brain and behavioral anomalies, providing insight into human neurodevelopmental disorders.Home-cage | stereotypic behavior | structural variation | brain MRI A ccumulating evidence suggests the importance of copy number variations (CNVs) in the etiology of neuropsychiatric disorders, including autism (1), schizophrenia (2-4), developmental delay (5), and other complex traits (6). The 16p11.2 region is particularly intriguing. Whereas deletion of 16p11.2 has been associated with autism (7-9), duplication of 16p11.2 has been associated with autism (9, 10) as well as schizophrenia (11). 16p11.2 CNVs have also been reported in patients with developmental delay, mental retardation, repetitive behaviors (12-16), and a highly penetrant form of obesity (17). A reciprocal effect of 16p11.2 dosage on head size has been noted, as deletions are associated with large head size or macrocephaly, whereas duplications are associated with microcephaly (16). These studies reveal the variability of symptoms in patients carrying the same 16p11.2 CNV, an extreme example being a family with three affected members with symptoms so heterogeneous that they were barely overlapping (18).Mouse models allow direct assessment of CNVs while reducing variability caused by genetic and environmental factors. We and others have previously used chromosome engineering (19) to model genetic alterations found in complex human diseases including cancer (20) and genomic disorders (21-24), allowing identification of the causative gene and elucidation of the mechanism involved (20,(25)(26)(27)). Here we used a similar approach to generate mouse models with deletion and duplication corresponding to those found in patients with 16p11.2 CNVs. Because of the evidence for clinical heterogeneity, we screened these models for multiple changes in brain anatomy and behavior by usin...

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Section: Resultsmentioning

confidence: 99%

Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism

Horev

Ellegood²,

Lerch³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

314

342

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“…These are conservative, but are performed at the expense of power. Therefore, instead, adaptive linear step-up procedures were adopted to control the false discovery rate (the expected proportion of false positives among significant results) at 5% (Benjamini, Krieger, & Yekutieli, 2006). Since a large number of our comparisons were highly significant (14/33 p ≤ .001), linear step-up resulted in an increase in the critical value required for significance.…”

Section: Home Literacy Environmentmentioning

confidence: 99%

Age and schooling effects on early literacy and phoneme awareness

Cunningham

Carroll

2011

Journal of Experimental Child Psychology

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Previous research on age and schooling effects is largely restricted to studies of children who begin formal schooling from the age of 6 and the measures of phoneme awareness used have typically lacked sensitivity for beginning readers. Our study addresses these issues by testing children aged 4-6 (first two years of formal schooling in the UK) on a sensitive dynamic measure of phoneme awareness and tests of early literacy. There were significant effects of both age and schooling on dynamic and static measures of phoneme awareness, word reading, spelling and letter-name knowledge but no significant age × time interactions. This indicates that older children within this age group generally outperform their younger classmates (although they do not make faster progress), and that this advantage is developed prior to the start of school.

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“…Apply the procedure of Benjamini and Hochberg (1995) with the α j defined in (5) replaced byα j = ĵ s 0 α * , whereŝ 0 = s − r. Benjamini et al (2006) prove that this procedure controls the FDR whenever the p-values satisfy (2) and are independent of each other. They also provide simulations which suggest that this procedure continues to control the FDR under positive dependence.…”

Section: Previous Methods For Control Of the Fdrmentioning

confidence: 99%

Control of the False Discovery Rate Under Dependence Using the Bootstrap and Subsampling

2008

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Control of the false discovery rate under dependence using the bootstrap and subsampling Romano, J P; Shaikh, A M; Wolf, M Romano, J P; Shaikh, A M; Wolf, M (2008). Control of the false discovery rate under dependence using the bootstrap and subsampling. Abstract This paper considers the problem of testing s null hypotheses simultaneously while controlling the false discovery rate (FDR). Benjamini and Hochberg (1995) provide a method for controlling the FDR based on p-values for each of the null hypotheses under the assumption that the p-values are independent. Subsequent research has since shown that this procedure is valid under weaker assumptions on the joint distribution of the p-values.Related procedures that are valid under no assumptions on the joint distribution of the p-values have also been developed. None of these procedures, however, incorporate information about the dependence structure of the test statistics. This paper develops methods for control of the FDR under weak assumptions that incorporate such information and, by doing so, are better able to detect false null hypotheses. We illustrate this property via a simulation study and two empirical applications. In particular, the bootstrap method is competitive with methods that require independence if independence holds, but it outperforms these methods under dependence.

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Adaptive linear step-up procedures that control the false discovery rate

Cited by 2,648 publications

References 23 publications

Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism

Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism

Age and schooling effects on early literacy and phoneme awareness

Control of the False Discovery Rate Under Dependence Using the Bootstrap and Subsampling

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