Abstract:
:Lander and Kruglyak [1995] gave guidelines for interpreting linkage results based on estimating how often a particular threshold for significance would be exceeded by chance in a single genome scan. What is unknown is how often two or more genome scans would exceed a particular threshold within the same region. We develop theoretical estimates of these values and compare these with the empirical estimates derived from the GAW11 data. For single-point analysis, the theoretical estimates predict the empirical estimates. For multipoint analysis, the theoretical values overestimate what is observed. For both single point and multipoint, modest p-values within a single genome scan may give highly significant results when replicated in the same region in other scans.
journal_name
Genet Epidemioljournal_title
Genetic epidemiologyauthors
Badner JA,Goldin LRdoi
10.1002/gepi.1370170778subject
Has Abstractpub_date
1999-01-01 00:00:00pages
S485-90eissn
0741-0395issn
1098-2272journal_volume
17 Suppl 1pub_type
杂志文章abstract::The present report summarizes findings on 670 cases of autosomal trisomy diagnosed in Scotland, with actual or expected dates of delivery in 1990 to 1994 inclusive. Cases were notified by cytogenetic service laboratories. There were 277 prenatal and 369 postnatal diagnoses and 24 spontaneous losses. Excluding the latt...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1999)16:2<179::AID-GEPI5>3
更新日期:1999-01-01 00:00:00
abstract::We set out to apply conventional analytic methods to a GAW data set of nuclear families with an oligogenic disease that has a population prevalence of 0.023. We chose methods generally applied to disorders with at least one major gene. Our approaches included: 1) complex segregation analysis under two models of ascert...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370120613
更新日期:1995-01-01 00:00:00
abstract::The recurrence risks for an X-linked disease with incomplete penetrance are evaluated for a sib given that an isolated proband (male or female) is affected. The derived formulae are applied to the X-linked form of Alport and fragile X syndromes. ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370030508
更新日期:1986-01-01 00:00:00
abstract::Site-specific familial aggregation and evidence supporting Mendelian codominant inheritance have been shown in lung cancer. In characterizing lung cancer families, a number of other cancers have been observed. The current study evaluates whether first-degree relatives of early onset lung cancer cases are at increased ...
journal_title:Genetic epidemiology
pub_type: 临床试验,杂志文章
doi:10.1002/(SICI)1098-2272(199911)17:4<274::AID-GEPI3
更新日期:1999-11-01 00:00:00
abstract::The transmission disequilibrium test (TDT), originally developed for mapping disease genes, has recently been extended to identify quantitative trait loci (QTL). For quantitative traits important for human health, generally multiple QTLs are involved. In the investigation of the statistical properties of the TDT, back...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1032
更新日期:2001-11-01 00:00:00
abstract::To better understand the contribution of major gene influences to individual differences in cardiovascular reactivity, we performed a segregation analysis on blood pressure responses to two laboratory tasks, mental arithmetic and bicycle exercise. The study population consisted of 1,451 adults (age > or = 18 years) wh...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1997)14:1<35::AID-GEPI3>3.
更新日期:1997-01-01 00:00:00
abstract::Family-based designs enriched with affected subjects and disease associated variants can increase statistical power for identifying functional rare variants. However, few rare variant analysis approaches are available for time-to-event traits in family designs and none of them applicable to the X chromosome. We develo...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22054
更新日期:2017-09-01 00:00:00
abstract::We used a case-control design to scan the genome for any associations between genetic markers and disease susceptibility loci using the first two replicates of the Mycenaean population from the GAW11 (Problem 2) data. Using a case-control approach, we constructed a series of 2-by-3 tables for each allele of every mark...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.13701707128
更新日期:1999-01-01 00:00:00
abstract::Testing for association between two random vectors is a common and important task in many fields, however, existing tests, such as Escoufier's RV test, are suitable only for low-dimensional data, not for high-dimensional data. In moderate to high dimensions, it is necessary to consider sparse signals, which are often ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22059
更新日期:2017-11-01 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::In diseases with a complex mode of inheritance, families with multiple affected individuals are difficult to ascertain. The haplotype sharing statistic (HSS) uses (hidden) co-ancestry between affected individuals from a founder population. These affected individuals will likely not only share the same mutation(s), but...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1997)14:6<915::AID-GEPI59>
更新日期:1997-01-01 00:00:00
abstract::We describe an extension to the TDT (transmission/disequilibrium test) which allows for more than two marker alleles and for covariates measured on the parent or offspring. We also describe a systematic genomic search where the mod score (maximized lod score) is computed for each marker under constraints on the popula...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370120623
更新日期:1995-01-01 00:00:00
abstract::Monte Carlo methods for linkage and segregation analysis are applied to the HGAR1 pedigree. To address these data, the methods are extended in several ways. The results are compared with those provided by PAP. ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370100658
更新日期:1993-01-01 00:00:00
abstract::Genes with imprinting (parent-of-origin) effects express differently when inheriting from the mother or from the father. Some genes for development and behavior in mammals are known to be imprinted. We developed parametric linkage analysis that accounts for imprinting effects for continuous traits, implementing it in ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20321
更新日期:2008-07-01 00:00:00
abstract::The large number of tests performed in analyzing data from genome-wide association studies has a large impact on the power of detecting risk variants, and analytic strategies specifying the optimal set of hypotheses to be tested are necessary. We propose a genome-wide strategy that is based on one degree of freedom te...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20182
更新日期:2006-12-01 00:00:00
abstract::The asymptotic distribution of [MOD] scores under the null hypothesis of no linkage is only known for affected sib pairs and other types of affected relative pairs. We have extended the GENEHUNTER-MODSCORE program to allow for simulations under the null hypothesis of no linkage to determine the empirical significance ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20264
更新日期:2008-01-01 00:00:00
abstract::Complex traits have been modeled under various modes of two-locus inheritance. One example of a two-locus threshold model is the situation where an individual is susceptible to a disease trait if he or she carries three or more disease alleles. Under this model, if each locus is examined individually the inheritance a...
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(1997)14:6<1097::AID-GEPI89
更新日期:1997-01-01 00:00:00
abstract::Genetic association studies of obstetric complications may genotype case and control mothers, or their respective newborns, or both case-control mothers and their children. The relatively high prevalence of many obstetric complications and the availability of both maternal and offspring's genotype data have provided m...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20406
更新日期:2009-09-01 00:00:00
abstract::Two analytic methods were used in the Problem 2 data set. First, generalized estimating equations (GEE) modelling was developed to adjust for familial correlation in regressions evaluating candidate genes and an environmental factor. Second, the affected-pedigree-member (APM) method was used to identify chromosomal re...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370120633
更新日期:1995-01-01 00:00:00
abstract::Intended to resolve the problem of constructing a matched population-based control sample, haplotype relative risk techniques frequently suffer from loss of power for late-onset diseases due to unavailability of parental genotypes that are required to form parent-offspring pairs. However, much of this missing informat...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1998)15:5<471::AID-GEPI3>3
更新日期:1998-01-01 00:00:00
abstract::The linkage between electronic health records (EHRs) and genotype data makes it plausible to study the genetic susceptibility of a wide range of disease phenotypes. Despite that EHR-derived phenotype data are subjected to misclassification, it has been shown useful for discovering susceptible genes, particularly in th...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22080
更新日期:2017-12-01 00:00:00
abstract::There has been extensive literature on modeling gene-gene interaction (GGI) and gene-environment interaction (GEI) in case-control studies with limited literature on statistical methods for GGI and GEI in longitudinal cohort studies. We borrow ideas from the classical two-way analysis of variance literature to address...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21744
更新日期:2013-09-01 00:00:00
abstract::It is believed that interactions among genes (epistasis) may play an important role in susceptibility to common diseases (Moore and Williams [2002]. Ann Med 34:88-95; Ritchie et al. [2001]. Am J Hum Genet 69:138-147). To study the underlying genetic variants of diseases, genome-wide association studies (GWAS) that sim...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20514
更新日期:2010-09-01 00:00:00
abstract::To explain the association between HLA-DRB1 gene and rheumatoid arthritis (RA), two main hypotheses have been proposed. The first, the shared epitope hypothesis, assumes a direct role of DRB1 in RA susceptibility. The second hypothesis assumes a recessive disease susceptibility gene in linkage disequilibrium with DRB1...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1998)15:4<419::AID-GEPI7>3
更新日期:1998-01-01 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::We performed multivariate genetic analyses of cardiovascular risk factors from two sets of data on US and Australian female twins. Similar models for body mass index (BMI), serum low density (LDL) and high density (HDL) lipoproteins, including age as a covariate, were fitted successfully to both groups. These suggeste...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370100638
更新日期:1993-01-01 00:00:00
abstract::We address the analytical problem of evaluating the evidence for linkage at a test locus while taking into account the effect of a known linked disease locus. The method we propose is a multimarker regression approach that models the identity-by-descent states for affected sib-pairs at a series of linked markers in te...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20137
更新日期:2006-04-01 00:00:00
abstract::Variable selection is growing in importance with the advent of high throughput genotyping methods requiring analysis of hundreds to thousands of single nucleotide polymorphisms (SNPs) and the increased interest in using these genetic studies to better understand common, complex diseases. Up to now, the standard approa...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20353
更新日期:2009-01-01 00:00:00
abstract::The 4 allele of apolipoprotein E (APOE) is associated with increased risk of two major causes of death in low-mortality populations: ischemic heart disease and Alzheimer's disease. It is less common among centenarians than at younger ages. Therefore, it is likely that it is associated with excess risk of death. This a...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.0164
更新日期:2002-02-01 00:00:00
abstract::We have conducted a simulation study in small pedigrees to investigate the power to detect linkage and heterogeneity for a disorder due to either one of two independent disease loci. We have considered a highly polymorphic marker locus (PIC = 70%) linked to one disease locus and unlinked to the second. The power to de...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370070306
更新日期:1990-01-01 00:00:00