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 contribute to disease risk. In this setting, the phenotypes of relatives are correlated even after adjustment for the genotypes of any one gene (residual correlation). Many methods have been proposed to address this problem, but their performance has not been evaluated systematically. In simulations we generated genotypes for a rare (frequency 0.35%) allele of moderate penetrance, and a common (frequency 15%) allele of low penetrance, and then generated correlated disease survival times using the Clayton-Oakes copula model. We ascertained families using both population and clinic designs. We then compared the estimates of several methods to the optimal ones obtained from the model used to generate the data. We found that penetrance estimates for common low-risk genotypes were more robust to model misspecification than those for rare, moderate-risk genotypes. For the latter, penetrance estimates obtained ignoring residual disease correlation had large biases. Also biased were estimates based only on families that segregate the risk allele. In contrast, a method for accommodating phenotype correlation by assuming the presence of genetic heterogeneity performed nearly optimally, even when the survival data were coded as binary outcomes. We conclude that penetrance estimates that accommodate residual phenotype correlation (even only approximately) outperform those that ignore it, and that coding censored survival outcomes as binary does not substantially increase the mean-square error of the estimates, provided the censoring is not extensive.
journal_name
Genet Epidemioljournal_title
Genetic epidemiologyauthors
Gong G,Hannon N,Whittemore ASdoi
10.1002/gepi.20493subject
Has Abstractpub_date
2010-05-01 00:00:00pages
373-81issue
4eissn
0741-0395issn
1098-2272journal_volume
34pub_type
杂志文章abstract::When many correlated traits are measured the potential exists to discover the coordinated control of these traits via genotyped polymorphisms. A common statistical approach to this problem involves assessing the relationship between each phenotype and each single nucleotide polymorphism (SNP) individually (PHN); and t...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20257
更新日期:2008-01-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is a complex disease which is partly determined by genetic factors which influence susceptibility to the disease phenotype. In this association study we try to define the high risk haplotypes which are responsible for this disease, together with other environmental factors. In many o...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370080607
更新日期:1991-01-01 00:00:00
abstract::The purpose of this commentary is to provide a framework for using the well-known sib-pair methodology in the context of epidemiologic study designs. Using examples from the Pittsburgh family studies of insulin-dependent diabetes mellitus, we illustrate that the sib-pair method can be used in family-based epidemiologi...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370080408
更新日期:1991-01-01 00:00:00
abstract::In traits suspected to be governed by at least two loci, linkage analysis incorporating the joint action of both loci may improve the power to detect linkage, increase the precision of estimating locus positions and provide insight into the underlying etiological mechanism. Recently, we mapped two susceptibility loci ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20190
更新日期:2007-01-01 00:00:00
abstract::The aim of this population-based study was to determine whether asthma aggregates in families, and if so, whether aggregation was consistent with environmental and/or genetic etiologies. Data were from 7,394 nuclear families (41,506 individuals) from the 1968 Tasmanian Asthma Survey, in which all Tasmanian schoolchild...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1997)14:3<317::AID-GEPI9>3
更新日期:1997-01-01 00:00:00
abstract::We examined the power of the stepwise iterated generalized least squares (GLS) method by modeling the relationship between quantitative traits and other variables using the simulated data for Problem 2A. The comparison between the generating model provided by the workshop and the results of the stepwise iterated GLS m...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1997)14:6<797::AID-GEPI39>
更新日期:1997-01-01 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::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::Apolipoprotein A-IV (APO A-IV) is a major protein component of mesenteric lymph chylomicrons and very-low-density lipoproteins. It is found in plasma predominantly unassociated with major lipoprotein fractions and in high density lipoproteins. APO A-IV exhibits structural heterogeneity owing to two codominant alleles,...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370060404
更新日期:1989-01-01 00:00:00
abstract::The univariate analysis of categorical twin data can be performed using either structural equation modeling (SEM) or logistic regression. This paper presents a comparison between these two methods using a simulation study. Dichotomous and ordinal (three category) twin data are simulated under two different sample size...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1996)13:1<79::AID-GEPI7>3.
更新日期:1996-01-01 00:00:00
abstract::This study is an investigation of the relationship between apolipoprotein E (apoE) phenotype, arterial disease, and mortality in a group of women (n = 1,751) aged 65 years and older enrolled in the Study of Osteoporotic Fractures. Crude mortality rates were highest among women with the 4-3 and 4-4 phenotypes but age-a...
journal_title:Genetic epidemiology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/(SICI)1098-2272(1997)14:2<147::AID-GEPI4>3
更新日期:1997-01-01 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::Although next-generation DNA sequencing technologies have made rare variant association studies feasible and affordable, the development of powerful statistical methods for rare variant association studies is still under way. Most of the existing methods for rare variant association studies compare the number of rare ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21646
更新日期:2012-07-01 00:00:00
abstract::We present a range of modelling components designed to facilitate Bayesian analysis of genetic-association-study data. A key feature of our approach is the ability to combine different submodels together, almost arbitrarily, for dealing with the complexities of real data. In particular, we propose various techniques f...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20140
更新日期:2006-04-01 00:00:00
abstract::We examined familial resemblance and performed segregation analysis for the maximal expiratory flow rate at 50% of vital capacity (Vmax50) and the ratio of Vmax50 to forced vital capacity (FVC), based on data from 309 nuclear families with 1,045 individuals in the town of Humboldt, Saskatchewan, in 1993. Vmax50 is con...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1999)16:1<95::AID-GEPI8>3.
更新日期:1999-01-01 00:00:00
abstract::Genome-wide association studies of discrete traits generally use simple methods of analysis based on chi(2) tests for contingency tables or logistic regression, at least for an initial scan of the entire genome. Nevertheless, more power might be obtained by using various methods that analyze multiple markers in combin...
journal_title:Genetic epidemiology
pub_type:
doi:10.1002/gepi.20465
更新日期:2009-01-01 00:00:00
abstract::We propose a new approach to detect gene × gene joint action in genome-wide association studies (GWASs) for case-control designs. This approach offers an exhaustive search for all two-way joint action (including, as a special case, single gene action) that is computationally feasible at the genome-wide level and has r...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21779
更新日期:2014-01-01 00:00:00
abstract::Smoking has been observed to affect plasma sex hormones and body mass index. The relationship between smoking, body mass index, and plasma concentration of sex hormones was studied in normal adult male twins. The analyses were performed for between 150 and 159 twin pairs for whom hormonal data were available on both t...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370060303
更新日期:1989-01-01 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::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::Atopic disease is generally recognized to be familial, although specific genetic components have yet to be identified. High levels of a unique class of immunoglobulins, immunoglobulin E (IgE), have been shown to be associated with allergies. Several investigators have reported evidence indicating a recessive regulator...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370020402
更新日期:1985-01-01 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::Inaccurate genetic (or linkage) maps can reduce the power to detect linkage, increase type I error, and distort haplotype and relationship inference. To improve the accuracy of existing maps, I propose a meta-analysis-based method that combines independent map estimates into a single estimate of the linkage map. The m...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20221
更新日期:2007-07-01 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::To date, thousands of genetic variants to be associated with numerous human traits and diseases have been identified by genome-wide association studies (GWASs). The GWASs focus on testing the association between single trait and genetic variants. However, the analysis of multiple traits and single nucleotide polymorph...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22330
更新日期:2020-10-01 00:00:00
abstract::Human apolipoprotein A-IV (APO A-IV) exhibits a common protein polymorphism detectable by isoelectric focusing (IEF) due to a single base substitution at codon 360 which replaces the frequently occurring glutamine residue (allele 1) with histidine (allele 2). Recently, sequence analysis of the APO A-IV coding region h...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370090503
更新日期:1992-01-01 00:00:00
abstract::A major locus influencing apolipoprotein AI (apo AI) serum levels was detected using data from the Donner Laboratory Family Study. This locus accounts for 46% of the phenotypic variability in apo AI levels. Multivariate segregation analysis revealed that this major locus also has significant pleiotropic effects on the...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370100648
更新日期:1993-01-01 00:00:00
abstract::A highly significant familial aggregation of eosinophil levels (X2(3) = 38.00) was detected in a sample from three Brazilian populations with a high incidence of helminthic parasitism. The data were unable to resolve genetic or common environment causation due to the lack of environmental concomitant variables. Result...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370090305
更新日期:1992-01-01 00:00:00
abstract::Hybrid designs arose from an effort to combine the benefits of family-based and population-based study designs. A recently proposed hybrid approach augments case-parent triads with population-based control-parent triads, genotyping everyone except the control offspring. Including parents of controls substantially impr...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20365
更新日期:2009-02-01 00:00:00
abstract::We used data from a population based series of breast cancer patients to investigate the genetic models that can best explain familial breast cancer not due to the BRCA1 and BRCA2 genes. The data set consisted of 1,484 women diagnosed with breast cancer under age 55 registered in the East Anglia Cancer registry betwee...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1014
更新日期:2001-07-01 00:00:00