Abstract:
:Various statistical methods have been proposed to evaluate associations between measured genetic variants and disease, including some using family designs. For breast cancer and rare variants, we applied a modified segregation analysis method that uses the population cancer incidence and population-based case families in which a mutation is known to be segregating. Here we extend the method to a common polymorphism, and use a regressive logistic approach to model familial aggregation by conditioning each individual on their mother's breast cancer history. We considered three models: 1) class A regressive logistic model; 2) age-of-onset regressive logistic model; and 3) proportional hazards familial model. Maximum likelihood estimates were calculated using the software MENDEL. We applied these methods to data from the Australian Breast Cancer Family Study on the CYP17 5'UTR T-->C MspA1 polymorphism measured for 1,447 case probands, 787 controls, and 213 relatives of case probands found to have the CC genotype. Breast cancer data for first- and second-degree relatives of case probands were used. The three methods gave consistent estimates. The best-fitting model involved a recessive inheritance, with homozygotes being at an increased risk of 47% (95% CI, 28-68%). The cumulative risk of the disease up to age 70 years was estimated to be 10% or 22% for a CYP17 homozygote whose mother was unaffected or affected, respectively. This analytical approach is well-suited to the data that arise from population-based case-control-family studies, in which cases, controls and relatives are studied, and genotype is measured for some but not all subjects.
journal_name
Genet Epidemioljournal_title
Genetic epidemiologyauthors
Cui JS,Spurdle AB,Southey MC,Dite GS,Venter DJ,McCredie MR,Giles GG,Chenevix-Trench G,Hopper JLdoi
10.1002/gepi.10222subject
Has Abstractpub_date
2003-04-01 00:00:00pages
161-72issue
3eissn
0741-0395issn
1098-2272journal_volume
24pub_type
杂志文章abstract::This report investigates the power issue in applying the non-parametric linkage analysis of affected sib-pairs (ASP) [Kruglyak and Lander, 1995: Am J Hum Genet 57:439-454] to localize genes that contribute to human longevity using long-lived sib-pairs. Data were simulated by introducing a recently developed statistica...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.10304
更新日期:2004-04-01 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::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::Genetic epidemiology is a relatively new discipline that seeks to unravel the role of genetic factors and their interactions with environmental factors in the etiology of diseases, using population and family study approaches. To characterize the overall direction and emphasis of research strategies used in this field...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370100505
更新日期:1993-01-01 00:00:00
abstract::Emerging evidence suggests that a genetic variant can affect multiple phenotypes, especially in complex human diseases. Therefore, joint analysis of multiple phenotypes may offer new insights into disease etiology. Recently, many statistical methods have been developed for joint analysis of multiple phenotypes, includ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22263
更新日期:2020-01-01 00:00:00
abstract::Construction of multifactorial disease models from epidemiological findings and their application to disease pedigrees for risk prediction is nontrivial for all but the simplest of cases. Multifactorial Disease Risk Calculator is a web tool facilitating this. It provides a user-friendly interface, extending a reported...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22101
更新日期:2018-03-01 00:00:00
abstract::Three characteristics of genetic epidemiology that distinguish it from its parent disciplines are a focus on population-based research, a focus on the joint effects of genes and the environment, and the incorporation of the underlying biology of the disease into its conceptual models. These principles are illustrated ...
journal_title:Genetic epidemiology
pub_type:
doi:10.1002/1098-2272(200012)19:4<289::AID-GEPI2>3.0.C
更新日期:2000-12-01 00:00:00
abstract::Complex diseases are presumed to be the results of interactions of several genes and environmental factors, with each gene only having a small effect on the disease. Thus, the methods that can account for gene-gene interactions to search for a set of marker loci in different genes or across genome and to analyze these...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20304
更新日期:2008-05-01 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::Mapping of the human genome has the potential to transform the traditional methods of genetic epidemiology. The complete draft sequence of the 3.3 billion nucleotides comprising the genome is now available over the Internet, including the location and nearly complete sequence of the 26,000 to 31,000 protein-encoding g...
journal_title:Genetic epidemiology
pub_type: 杂志文章,评审
doi:10.1002/gepi.10226
更新日期:2003-02-01 00:00:00
abstract::Using a recently developed semiparametric method for combined linkage/linkage-disequilibrium analysis, we analyzed the Collaborative Study on the Genetics of Alcoholism data subset developed for Genetic Analysis Workshop 11 (GAW11). This semiparametric approach estimates recombination fractions for linkage, marker log...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370170708
更新日期:1999-01-01 00:00:00
abstract::Complex segregation analysis and linkage methods are mathematical techniques for the genetic dissection of complex diseases. They are used to delineate complex modes of familial transmission and to localize putative disease susceptibility loci to specific chromosomal locations. The computational problem of Bayesian li...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/1098-2272(2000)19:1+<::AID-GEPI8>3.0.CO;2-
更新日期:2000-01-01 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::Noncoding DNA contains gene regulatory elements that alter gene expression, and the function of these elements can be modified by genetic variation. Massively parallel reporter assays (MPRA) enable high-throughput identification and characterization of functional genetic variants, but the statistical methods to identi...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22337
更新日期:2020-10-01 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::Clinical trial results have recently demonstrated that inhibiting inflammation by targeting the interleukin-1β pathway can offer a significant reduction in lung cancer incidence and mortality, highlighting a pressing and unmet need to understand the benefits of inflammation-focused lung cancer therapies at the genetic...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22358
更新日期:2021-02-01 00:00:00
abstract::Methods to account for population structure (PS) in genome-wide association studies have been well developed in samples of unrelated individuals, but when a sample is composed of families, the task of finding and accounting for PS is not as straight forward. Family-based tests that condition on parental genotypes or t...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20590
更新日期:2011-09-01 00:00:00
abstract::Recently, testing for anticipation has received renewed interest. It is well known that standard statistical methods are inappropriate for this purpose due to problems of sampling bias. Few statistical tests have been proposed for comparing mean age of onset in affected parents with mean age of onset in affected child...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20057
更新日期:2005-04-01 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::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::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::Association analysis has led to the identification of many genetic variants for complex diseases. While assessing the association between genes and a disease, other factors can play an important role. The consequence of not considering covariates (such as population stratification and environmental factors) is well-do...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20558
更新日期:2011-02-01 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::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::This paper describes a general genetic model which encompasses both autosomal and X-linked inheritance as submodels. It allows one to test for X-linked inheritance of a trait by comparing the likelihood of X-linked inheritance to the likelihood of the general genetic model. The general model is formulated as two loci,...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370010105
更新日期:1984-01-01 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::Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) associated with complex traits. However, the genetic heritability of most of these traits remains unexplained. To help guide future studies, we address the crucial question of whether future GWAS can detect new SNP assoc...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21724
更新日期:2013-05-01 00:00:00
abstract::The recent successes of genome-wide association studies (GWAS) have renewed interest in genome environment wide interaction studies (GEWIS) to discover genetic factors that modulate penetrance of environmental exposures to human diseases. Indeed, gene-environment interactions (G × E), which have not been emphasized in...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21890
更新日期:2015-07-01 00:00:00
abstract::In case-control genetic association studies, the robust procedure, Pearson's Chi-square test, is commonly used for testing association between disease status and genetic markers. However, this test does not take the possible trend of relative risks, which are due to genotype, into account. On the contrary, although Co...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20615
更新日期:2011-11-01 00:00:00
abstract::As part of Genetic Analysis Workshop 17 (GAW17), our group considered the application of novel and standard approaches to the analysis of genotype-phenotype association in next-generation sequencing data. Our group identified a major issue in the analysis of the GAW17 next-generation sequencing data: type I error and ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20650
更新日期:2011-01-01 00:00:00