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 by a review of the genetic epidemiology of breast and ovarian cancer. Descriptive and mechanistic models for the joint effects of genes and "environmental" risk factors such as hormones and reproductive events are compared to illustrate the need to understand the biology. The contribution of population-based research to the development of the evidence for the involvement of major genes, the discovery of BRCA1 and BRCA2, and their characterization is reviewed. Interactions of major susceptibility genes, metabolic genes, and hormones are also discussed. I conclude with some suggestions for future directions for the field, the journal, and the Society, including recent bioethics initiatives. I believe that the Society should reach out more to the epidemiology community and that the journal should shift its emphasis from pure methodology to also include more substantive papers that illustrate these principles.
journal_name
Genet Epidemioljournal_title
Genetic epidemiologyauthors
Thomas DCdoi
10.1002/1098-2272(200012)19:4<289::AID-GEPI2>3.0.Csubject
Has Abstractpub_date
2000-12-01 00:00:00pages
289-300issue
4eissn
0741-0395issn
1098-2272pii
10.1002/1098-2272(200012)19:4<289::AID-GEPI2>3.0.Cjournal_volume
19pub_type
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::In this study, we compare the statistical properties of a number of methods for estimating P-values for allele-sharing statistics in non-parametric linkage analysis. Some of the methods are based on the normality assumption, using different variance estimation methods, and others use simulation (gene-dropping) to find...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20177
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::The use of patterned covariance matrices in forming pedigree-based mixed models for quantitative traits is discussed. It is suggested that patterned covariance matrix models provide intuitive, theoretically appealing, and flexible genetic modeling devices for pedigree data. It is suggested further that the very great ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370080104
更新日期:1991-01-01 00:00:00
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 dev...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370170778
更新日期:1999-01-01 00:00:00
abstract::Increasing evidence has shown that genes may cause prenatal, neonatal, and pediatric diseases depending on their parental origins. Statistical models that incorporate parent-of-origin effects (POEs) can improve the power of detecting disease-associated genes and help explain the missing heritability of diseases. In ma...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22060
更新日期:2017-11-01 00:00:00
abstract::HLA-A, -B, -C, -DR, and -DQ typings of the Schmiedeleut Hutterites of South Dakota were collected as part of an ongoing genetic-epidemiologic study of HLA and fertility. A total of 1,082 individuals, including 852 married adults representative of the reproductive population of this isolate, were characterized for five...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370120106
更新日期:1995-01-01 00:00:00
abstract::We develop a Bayesian multi-SNP Markov chain Monte Carlo approach that allows published functional significance scores to objectively inform single nucleotide polymorphism (SNP) prior effect sizes in expression quantitative trait locus (eQTL) studies. We developed the Normal Gamma prior to allow the inclusion of funct...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21961
更新日期:2016-05-01 00:00:00
abstract::We propose methods to construct meiotic gene maps while controlling the probability of a decision-error. First, a single step gene ordering procedure is presented whose decision-error probability is bounded above by a prespecified threshold. The bound for the error probability is valid under quite general circumstance...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1999)16:3<274::AID-GEPI4>3
更新日期:1999-01-01 00:00:00
abstract::Different maximum likelihood approaches were used to explore the role of candidate genes in the variability of quantitative trait Q1 while accounting for the effects of age, Q2, and Q3. Segregation analysis, under the class D regressive model, provides evidence for a Mendelian gene effect on the adjusted trait Q1. Res...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370120643
更新日期:1995-01-01 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 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::Allele frequencies are generally estimated with data on a set of unrelated individuals. In genetic studies of late-onset diseases, the founding individuals in pedigrees are often not available, and so one is confronted with the problem of estimating allele frequencies with data on related individuals. We focus on sibp...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.2
更新日期:2001-04-01 00:00:00
abstract::The aim of this paper is to generalize permutation methods for multiple testing adjustment of significant partial regression coefficients in a linear regression model used for microarray data. Using a permutation method outlined by Anderson and Legendre [1999] and the permutation P-value adjustment from Simon et al. [...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20255
更新日期:2008-01-01 00:00:00
abstract::The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between mark...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20400
更新日期:2009-09-01 00:00:00
abstract::Imputation is widely used for obtaining information about rare variants. However, one issue concerning imputation is the low accuracy of imputed rare variants as the inaccurate imputed rare variants may distort the results of region-based association tests. Therefore, we developed a pre-collapsing imputation method (P...
journal_title:Genetic epidemiology
pub_type: 杂志文章,多中心研究
doi:10.1002/gepi.22020
更新日期:2017-01-01 00:00:00
abstract::Meta-analyses of genetic association studies are usually performed using a single polymorphism at a time, even though in many cases the individual studies report results from partially overlapping sets of polymorphisms. We present here a multipoint (or multilocus) method for multivariate meta-analysis of published pop...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20531
更新日期:2010-11-01 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::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::The participants of Presentation Group 18 of Genetic Analysis Workshop 14 analyzed the Collaborative Study on the Genetics of Alcoholism data set to investigate sex-specific effects for phenotypes related to alcohol dependence. In particular, the participants looked at imprinting (which is also known as parent-of-orig...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20121
更新日期:2005-01-01 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::Association tests of multilocus haplotypes are of interest both in linkage disequilibrium mapping and in candidate gene studies. For case-parent trios, I discuss the extension of existing multilocus methods to include ambiguous haplotypes in tests of models which distinguish between the cis and trans phase. A likeliho...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.10252
更新日期:2003-09-01 00:00:00
abstract::Alcohol dependence often is a familial disorder and has a genetic component. Research in causative factors of alcoholism is coordinated by a multi-center program, COGA [The Collaborative Study on the Genetics of Alcoholism, Begleiter et al., 1995]. We analyzed a subset of the COGA family sample, 84 pedigrees of Caucas...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370170768
更新日期:1999-01-01 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::We investigated a variety of methods for pooling data from eight data sets (n = 5,424 subjects) to validate evidence for linkage of markers in the cytokine cluster on chromosome 5q31-33 to asthma and asthma-associated phenotypes. Chromosome 5 markers were integrated into current genetic linkage and physical maps, and ...
journal_title:Genetic epidemiology
pub_type: 杂志文章,meta分析
doi:10.1002/gepi.2001.21.s1.s103
更新日期:2001-01-01 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
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::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::We investigated the independent contributions of a candidate gene and an environmental factor, and the presence of gene x environment (G x E) interaction, in the etiology of a disease in the Genetic Analysis Workshop (GAW) 12 problem 2 simulated data using a two-stage approach utilizing both case-control and case-pare...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.2001.21.s1.s843
更新日期:2001-01-01 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