Abstract:
:With the rise of both the number and the complexity of traits of interest, control of the false discovery rate (FDR) in genetic association studies has become an increasingly appealing and accepted target for multiple comparison adjustment. While a number of robust FDR-controlling strategies exist, the nature of this error rate is intimately tied to the precise way in which discoveries are counted, and the performance of FDR-controlling procedures is satisfactory only if there is a one-to-one correspondence between what scientists describe as unique discoveries and the number of rejected hypotheses. The presence of linkage disequilibrium between markers in genome-wide association studies (GWAS) often leads researchers to consider the signal associated to multiple neighboring SNPs as indicating the existence of a single genomic locus with possible influence on the phenotype. This a posteriori aggregation of rejected hypotheses results in inflation of the relevant FDR. We propose a novel approach to FDR control that is based on prescreening to identify the level of resolution of distinct hypotheses. We show how FDR-controlling strategies can be adapted to account for this initial selection both with theoretical results and simulations that mimic the dependence structure to be expected in GWAS. We demonstrate that our approach is versatile and useful when the data are analyzed using both tests based on single markers and multiple regression. We provide an R package that allows practitioners to apply our procedure on standard GWAS format data, and illustrate its performance on lipid traits in the North Finland Birth Cohort 66 cohort study.
journal_name
Geneticsjournal_title
Geneticsauthors
Brzyski D,Peterson CB,Sobczyk P,Candès EJ,Bogdan M,Sabatti Cdoi
10.1534/genetics.116.193987subject
Has Abstractpub_date
2017-01-01 00:00:00pages
61-75issue
1eissn
0016-6731issn
1943-2631pii
genetics.116.193987journal_volume
205pub_type
杂志文章相关文献
GENETICS文献大全abstract::We have investigated the order of the four genes cyc1, rad7, SUP4, and cdc8 which form a tightly linked cluster on the right arm of chromosome X in the yeast Saccharomyces cerevisiae. Crossing over and coconversion data from tetrad analysis established the gene order to be centromere-cyc1-rad7-SUP4. Also cdc8 appeared...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1975-12-01 00:00:00
abstract::Early embryogenesis in Drosophila melanogaster is controlled by maternal gene products, which are deposited in the egg during oogenesis. It is not well understood how maternal gene expression is controlled during germline development. pipsqueak (psq) is a complex locus that encodes several nuclear protein variants con...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.110.121624
更新日期:2011-02-01 00:00:00
abstract::We have established the DNA sequence and analyzed the transcription and translation products of a series of putative nodulation (nod) genes in Rhizobium meliloti strain 1021. Four loci have been designated nodF, nodE, nodG and nodH. The correlation of transposon insertion positions with phenotypes and open reading fra...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::Our understanding of the cellular mechanisms by which animals regulate their response to starvation is limited, despite the strong relevance of the problem to major human health issues. The L1 diapause of Caenorhabditis elegans, where first-stage larvae arrest in response to a food-less environment, is an excellent sy...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.116.194282
更新日期:2017-02-01 00:00:00
abstract::The X chromosome requires special treatment in the mapping of quantitative trait loci (QTL). However, most QTL mapping methods, and most computer programs for QTL mapping, have focused exclusively on autosomal loci. We describe a method for appropriate treatment of the X chromosome for QTL mapping in experimental cros...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.106.061176
更新日期:2006-12-01 00:00:00
abstract::Haplotype variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase (LPL) gene was scored in three populations: African-Americans from Jackson, Mississippi (24 individuals), Finns from North Karelia, Finland (24), and non-Hispanic whites from Rochester, Minnesota (23). Earlier analyses had indicate...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::Stem cells have a fascinating biology and offer great prospects for therapeutic applications, stimulating intense research on what controls their properties and behavior. Although there have been significant advances in our understanding of how local microenvironments, or niches, control the maintenance and activity o...
journal_title:Genetics
pub_type: 杂志文章,评审
doi:10.1534/genetics.108.098244
更新日期:2008-12-01 00:00:00
abstract::The long terminal repeat retrotransposon, Magnaporthe gypsy-like element (MAGGY), has been shown to be targeted for cytosine methylation in a subset of Magnaporthe oryzae field isolates. Analysis of the F1 progeny from a genetic cross between methylation-proficient (Br48) and methylation-deficient (GFSI1-7-2) isolates...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.113.155978
更新日期:2013-11-01 00:00:00
abstract::Cell surface immunoglobulin superfamily (IgSF) proteins play important roles in the development and function of the nervous system . Here we define the role of a Caenorhabditis elegans IgSF protein, RIG-3, in the function of the AVA command interneuron. This study reveals that RIG-3 regulates the abundance of the glut...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.119.302872
更新日期:2020-01-01 00:00:00
abstract::The ade6-M26 mutation of Schizosaccharomyces pombe has previously been reported to stimulate ade6 intragenic meiotic recombination. We report here that the ade6-M26 mutation is a single G----T nucleotide change, that M26 stimulated recombination within ade6 but not at other distinct loci, and that M26 stimulated meiot...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
abstract::Two-dimensional paper chromatography was performed on methanol extracts of leaves of hexaploid bread wheat, Triticum aestivum L. em. Thell. cultivar Chinese Spring, and of the available nullisomic-tetrasomic compensating lines, the tetrasomic lines and the ditelocentric lines. The chromatograms had 27 spots identified...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
abstract::Mutator and antimutator alleles often arise and spread in both natural microbial populations and laboratory evolution experiments. The evolutionary dynamics of these mutation rate modifiers are determined by indirect selection on linked beneficial and deleterious mutations. These indirect selection pressures have been...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.116.193565
更新日期:2016-11-01 00:00:00
abstract::HO endonuclease-induced double-strand breaks (DSBs) within a direct duplication of Escherichia coli lacZ genes are repaired either by gene conversion or by single-strand annealing (SSA), with > 80% being SSA. Previously it was demonstrated that the RAD52 gene is required for DSB-induced SSA. In the present study, the ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
abstract::Considering a random mating population of finite size, the variance of the number of loci having a given gene frequency was derived under the assumption of a steady flux of mutations. The variance of average heterozygosity among populations was also derived under the same assumption. It was shown that these variances ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1973-02-01 00:00:00
abstract::RNA transcribed from the Saccharomyces cerevisiae retrotransposon Ty1 accumulates to a high level in mitotically growing haploid cells, yet transposition occurs at very low frequencies. The product of reverse transcription is a linear double-stranded DNA molecule that reenters the genome by either Ty1-integrase-mediat...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
abstract::The Sh2/A1 orthologous region of maize, rice, and sorghum contains five genes in the order Sh2, X1, X2, and two A1 homologs in tandem duplication. The Sh2 and A1 homologs are separated by approximately 20 kb in rice and sorghum and by approximately 140 kb in maize. We analyzed the fate of the Sh2/A1 region in large-ge...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2002-03-01 00:00:00
abstract::Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed indi...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.112.147330
更新日期:2013-04-01 00:00:00
abstract::A specific host-pathogen interaction exists between Caenorhabditis elegans and the gram-positive bacterium Microbacterium nematophilum. This bacterium is able to colonize the rectum of susceptible worms and induces a defensive tail-swelling response in the host. Previous mutant screens have identified multiple loci th...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.106.060087
更新日期:2007-02-01 00:00:00
abstract::Pairwise linkage disequilibrium values (D) were estimated for 14 allozyme loci in two natural populations of lodgepole pine (Pinus contorta ssp. latifolia). Maternal multilocus genotypes were inferred from samples of (haploid) megagametophytic seed-endosperms. Coupling/repulsion double heterozygotes were distinguished...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1987-02-01 00:00:00
abstract::Vertebrate retrotransposons have been used extensively for phylogenetic analyses and studies of molecular evolution. Information can be obtained from specific inserts either by comparing sequence differences that have accumulated over time in orthologous copies of that insert or by determining the presence or absence ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2001-06-01 00:00:00
abstract::Sister-chromatid exchanges (SCE) were studied in allium cepa L. meristematic cells at the second and third divisions after BrdUrd-substitution during just the first or during the second and third cycles, respectively. The observed SCE nonreciprocal/reciprocal ratios detected at the third division in both experiments, ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1979-08-01 00:00:00
abstract::Drosophila adult leg development provides an ideal model system for characterizing the molecular mechanisms of hormone-triggered morphogenesis. A pulse of the steroid hormone ecdysone at the onset of metamorphosis triggers the rapid transformation of a flat leg imaginal disc into an immature adult leg, largely through...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2003-11-01 00:00:00
abstract::The fixation of a beneficial allele in a population leaves a well-characterized signature in patterns of nucleotide variation at linked sites. This signature can be used to estimate the time since fixation from patterns of polymorphism in extant individuals. I introduce a method to assess the support in polymorphism d...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2003-08-01 00:00:00
abstract::Mutation of a CCG sequence in the 5'-untranslated region of the mitochondrially encoded cytochrome b mRNA in Saccharomyces cerevisiae results in destabilization of the message and respiratory deficiency of the mutant strain. This phenotype mimics that of a mutation in the nuclear CBP1 gene. Here it is shown that overe...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.104.036467
更新日期:2005-11-01 00:00:00
abstract::SNAP receptor (SNARE) and Sec1/Munc18 (SM) proteins are required for all intracellular membrane fusion events. SNAREs are widely believed to drive the fusion process, but the function of SM proteins remains unclear. To shed light on this, we screened for dominant-negative mutants of yeast Sec1 by random mutagenesis of...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.108.090423
更新日期:2008-09-01 00:00:00
abstract::Plants regenerated from tissue culture often display somaclonal variation, that is, somatic and often meiotically heritable phenotypic variation that can result from both genetic and epigenetic modifications. To better understand the molecular basis of somaclonal variation, we have characterized four unique tissue cul...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.110.117929
更新日期:2010-11-01 00:00:00
abstract::The genetic etiology of many complex diseases is highly heterogeneous. A complex disease can be caused by multiple mutations within the same gene or mutations in multiple genes at various genomic loci. Although these disease-susceptibility mutations can be collectively common in the population, they are often individu...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.118.301266
更新日期:2018-10-01 00:00:00
abstract::The Mus101 family of chromosomal proteins, identified initially in Drosophila, is widely conserved and has been shown to function in a variety of DNA metabolic processes. Such functions include DNA replication, DNA damage repair, postreplication repair, damage checkpoint activation, chromosome stability, and chromosom...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.104.036137
更新日期:2005-03-01 00:00:00
abstract::Heteroduplexes with single base pair mismatches of known sequence were prepared by annealing separated strands of bacteriophage lambda DNA and used to transfect Escherichia coli. A series of transition (G:T and A:C) and transversion (G:A and C:T) mismatches located throughout most of the bacteriophage lambda cI gene h...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1987-04-01 00:00:00
abstract::Fossil evidence links human ancestry with populations that evolved from modern gracile morphology in Africa 130,000-160,000 years ago. Yet fossils alone do not provide clear answers to the question of whether the ancestors of all modern Homo sapiens comprised a single African population or an amalgamation of distinct ...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.105.041095
更新日期:2005-08-01 00:00:00