Abstract:
:Due to the drop in sequencing cost, the number of sequenced genomes is increasing rapidly. To improve power of rare-variant tests, these sequenced samples could be used as external control samples in addition to control samples from the study itself. However, when using external controls, possible batch effects due to the use of different sequencing platforms or genotype calling pipelines can dramatically increase type I error rates. To address this, we propose novel summary statistics based single and gene- or region-based rare-variant tests that allow the integration of external controls while controlling for type I error. Our approach is based on the insight that batch effects on a given variant can be assessed by comparing odds ratio estimates using internal controls only vs. using combined control samples of internal and external controls. From simulation experiments and the analysis of data from age-related macular degeneration and type 2 diabetes studies, we demonstrate that our method can substantially improve power while controlling for type I error rate.
journal_name
Genet Epidemioljournal_title
Genetic epidemiologyauthors
Lee S,Kim S,Fuchsberger Cdoi
10.1002/gepi.22057subject
Has Abstractpub_date
2017-11-01 00:00:00pages
610-619issue
7eissn
0741-0395issn
1098-2272journal_volume
41pub_type
杂志文章abstract::Penalized regression methods offer an attractive alternative to single marker testing in genetic association analysis. Penalized regression methods shrink down to zero the coefficient of markers that have little apparent effect on the trait of interest, resulting in a parsimonious subset of what we hope are true perti...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20543
更新日期:2010-12-01 00:00:00
abstract::It has been suggested that collections of affected sib pairs, or their nuclear families, may be an efficient method for screening for genetic linkages in schizophrenia. We present the data collected in five years from 15 hospitals in the state of Maryland in an effort to determine if such a collection scheme will be f...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370060604
更新日期:1989-01-01 00:00:00
abstract::This paper summarizes the analyses by participants in the insulin-dependent diabetes mellitus (IDDM) component of Genetic Analysis Workshop 5 (GAW5). The data were obtained from 94 families with two or more IDDM sibs. Topics treated in the Workshop analysis included the following: methods for detecting associations an...
journal_title:Genetic epidemiology
pub_type: 杂志文章,评审
doi:10.1002/gepi.1370060111
更新日期:1989-01-01 00:00:00
abstract::Contributions to Group 17 of the Genetic Analysis Workshop 15 considered dense markers in linkage disequilibrium (LD) in the context of either linkage or association analysis. Three contributions reported on methods for modeling LD or selecting a subset of markers in linkage equilibrium to perform linkage analysis. Wh...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20291
更新日期:2007-01-01 00:00:00
abstract::alpha 1-antitrypsin (alpha 1 AT) deficiency is variably associated with the development of pulmonary emphysema. To gain insight into the process which begins the Z point mutation at the Protease Inhibitor (Pi) locus and results in the variable development of emphysema, three quantitative phenotypes, including total al...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370070204
更新日期:1990-01-01 00:00:00
abstract::Elevation in plasma total homocysteine (tHcy) is believed to be causally related to cardiovascular disease. Like age and sex, the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR(C677T)) is an important nonmodifiable determinant of tHcy, which may be considered when describing normal ranges of tHcy i...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.10239
更新日期:2003-05-01 00:00:00
abstract::Healthy male monozygotic (MZ) and dizygotic (DZ) twin pairs (MZ pairs = 77; DZ pairs = 88) were studied to assess the effect of dietary intake, physical activity, physical fitness, body mass index (BMI), sum of the triceps and subscapular skinfold measurements, alcohol and caffeine consumption, and smoking patterns on...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370050409
更新日期:1988-01-01 00:00:00
abstract::The extended transmission disequilibrium test (ETDT) of Sham and Curtis [1995] is a powerful test of the null hypothesis of no linkage between a multi-allelic marker locus and a disease susceptibility locus of unknown location in the presence of association between alleles at the two loci. We propose a generalization ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.13701707108
更新日期:1999-01-01 00:00:00
abstract::Understanding the genetic background of complex diseases and disorders plays an essential role in the promising precision medicine. The evaluation of candidate genes, however, requires time-consuming and expensive experiments given a large number of possibilities. Thus, computational methods have seen increasing appli...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22282
更新日期:2020-06-01 00:00:00
abstract::Several methods have been proposed to increase power in rare variant association testing by aggregating information from individual rare variants (MAF < 0.005). However, how to best combine rare variants across multiple ethnicities and the relative performance of designs using different ethnic sampling fractions remai...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21939
更新日期:2016-01-01 00:00:00
abstract::Grade of membership analysis (GoM) may have particular relevance for genetic epidemiology. The method can flexibly relate genetic markers, clinical features, and environmental exposures to possible subtypes of disease termed pure types even when population allele frequencies and penetrance functions are not known. Hen...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370100628
更新日期:1993-01-01 00:00:00
abstract::Rheumatoid arthritis is an inflammatory disease for which positive associations have been described with some HLA-DRB1 alleles. The associated alleles share a similar amino acid sequence in the third hypervariable region, the shared epitope, but differ at position 71 and 86. It has been suggested that HLA susceptibili...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/1098-2272(200012)19:4<422::AID-GEPI12>3.0.
更新日期:2000-12-01 00:00:00
abstract::Linkage analysis of complex traits has had limited success in identifying trait-influencing loci. Recently, coding variants have been implicated as the basis for some biomedical associations. We tested whether coding variants are the basis for linkage peaks of complex traits in 42 African-American (n = 596) and 90 His...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21801
更新日期:2014-05-01 00:00:00
abstract::There has been a great interest and a few successes in the identification of complex disease susceptibility genes in recent years. Association studies, where a large number of single-nucleotide polymorphisms (SNPs) are typed in a sample of cases and controls to determine which genes are associated with a specific dise...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20041
更新日期:2005-02-01 00:00:00
abstract::Genome-wide association (GWA) studies have proved extremely successful in identifying novel genetic loci contributing effects to complex human diseases. In doing so, they have highlighted the fact that many potential loci of modest effect remain undetected, partly due to the need for samples consisting of many thousan...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20482
更新日期:2010-05-01 00:00:00
abstract::Genetic Analysis Workshop 17 (GAW17) focused on the transition from genome-wide association study designs and methods to the study designs and statistical genetic methods that will be required for the analysis of next-generation sequence data including both common and rare sequence variants. In the 166 contributions t...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20659
更新日期:2011-01-01 00:00:00
abstract::Family data are useful for estimating disease risk in carriers of specific genotypes of a given gene (penetrance). Penetrance is frequently estimated assuming that relatives' phenotypes are independent, given their genotypes for the gene of interest. This assumption is unrealistic when multiple shared risk factors con...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20493
更新日期:2010-05-01 00:00:00
abstract::The research presented in group 11 of the Genetic Analysis Workshop 15 (GAW15) falls into two major themes: Model selection approaches for gene mapping (both Bayesian and Frequentist); and other Bayesian methods. These methods either allow relaxation of some of the common assumptions, such as mode of inheritance, for ...
journal_title:Genetic epidemiology
pub_type: 杂志文章,评审
doi:10.1002/gepi.20285
更新日期:2007-01-01 00:00:00
abstract::Recent studies have found an association between presence of apolipoprotein E (APOE) epsilon 4 allele and Alzheimer's disease (AD). The present study compared the cumulative risk of primary progressive dementia (PPD) in relatives of AD probands carrying at least one copy of the epsilon 4 allele with the relatives of A...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1996)13:3<285::AID-GEPI5>3
更新日期:1996-01-01 00:00:00
abstract::A major locus that determines levels of apolipoprotein B (apoB) was revealed by likelihood analysis on 331 members of 36 pedigrees. The major locus explained 43.2% of the observed variance, with the remainder attributed to random environmental factors. Estimated mean apoB levels (mg/dl) were 110.5 +/- 2.5, 141.9 +/- 4...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370040202
更新日期:1987-01-01 00:00:00
abstract::The multiplicity problem has become increasingly important in genetic studies as the capacity for high-throughput genotyping has increased. The control of False Discovery Rate (FDR) (Benjamini and Hochberg. [1995] J. R. Stat. Soc. Ser. B 57:289-300) has been adopted to address the problems of false positive control an...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20164
更新日期:2006-09-01 00:00:00
abstract::The purpose of the current study was to utilize the Genetic Analysis Workshop 12 simulated data to evaluate fine-mapping strategies for quantitative traits. We approached the analysis as if it was a follow-up to a genome scan that had identified two regions of interest and used the provided 1-cM density microsatellite...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.2001.21.s1.s467
更新日期:2001-01-01 00:00:00
abstract::Jewish women have been reported to have a higher risk for familial breast cancer than non-Jewish women and to be more likely to carry mutations in breast cancer genes such as BRCA1. Because BRCA1 mutations also increase women's risk for ovarian cancer, we asked whether Jewish women are at higher risk for familial ovar...
journal_title:Genetic epidemiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/(SICI)1098-2272(1998)15:1<51::AID-GEPI4>3.
更新日期:1998-01-01 00:00:00
abstract::Our group studied the effects of genotyping errors, pedigree errors, and missing data on a wide range of techniques, with a focus on the role of single-nucleotide polymorphisms (SNPs). Half of our group used simulated data, and half of our group used data from the Collaborative Study on the Genetics of Alcoholism (COG...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20120
更新日期:2005-01-01 00:00:00
abstract::It is possible to estimate the proportionate contributions of ancestral populations to admixed individuals or populations using genetic markers, but different loci and alleles vary considerably in the amount of information that they provide. Conventionally, the allele frequency difference between parental populations ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.10319
更新日期:2004-05-01 00:00:00
abstract::For many clinical studies in cancer, germline DNA is prospectively collected for the purpose of discovering or validating single-nucleotide polymorphisms (SNPs) associated with clinical outcomes. The primary clinical endpoint for many of these studies are time-to-event outcomes such as time of death or disease progres...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21645
更新日期:2012-09-01 00:00:00
abstract::Increased adiposity has repeatedly been identified as a major risk factor for a variety of chronic diseases. However, the question still remains whether the amount of adipose tissue itself is genetically mediated. To address this question, a segregation analysis, using maximum likelihood techniques as implemented in t...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370120505
更新日期:1995-01-01 00:00:00
abstract::To evaluate the risk of a disease associated with the joint effects of genetic susceptibility and environmental exposures, epidemiologic researchers often test for non-multiplicative gene-environment effects from case-control studies. In this article, we present a comparative study of four alternative tests for intera...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20337
更新日期:2008-11-01 00:00:00
abstract::An extension of the traditional regression of offspring on midparent (ROMP) method was used to estimate the heritability of the trait, test for marker association, and estimate the heritability attributable to a marker locus. The fifty replicates of the Genetic Analysis Workshop (GAW) 12 simulated general population d...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.2001.21.s1.s794
更新日期:2001-01-01 00:00:00
abstract::GAW10 Problem 2 involves a simulated common disease defined by imposing a threshold, T, on a quantitative trait, Q1. Every individual with a value of Q1 > or = T (where T = 40) is defined as affected. Also thought to be associated with the disease as intervening variables are four other quantitative traits (Q2, Q3, Q4...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1997)14:6<737::AID-GEPI29>
更新日期:1997-01-01 00:00:00