Abstract:
:Given the rapid pace with which genomics and other -omics disciplines are evolving, it is sometimes necessary to shift down a gear to consider more general scientific questions. In this line, in my presidential address I formulate six questions for genetic epidemiologists to ponder on. These cover the areas of reproducibility, statistical significance, chance findings, precision medicine and related fields such as bioinformatics and data science. Possible hints at responses are presented to foster our further discussion of these topics.
journal_name
Genet Epidemioljournal_title
Genetic epidemiologyauthors
König IRdoi
10.1002/gepi.22191subject
Has Abstractpub_date
2019-04-01 00:00:00pages
242-249issue
3eissn
0741-0395issn
1098-2272journal_volume
43pub_type
杂志文章abstract::Unaffected individuals are often disregarded in nonparametric linkage analysis. Because of the presumed high complexity of genetic interactions and the resulting low penetrance of any single genetic effect, the statistical contribution of unaffected sib pairs is thought to be considerably lower than that of the affect...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.2001.21.s1.s522
更新日期:2001-01-01 00:00:00
abstract::Our aim was to develop a simple method for testing gene-environment interaction in twin data ascertained through affected twins (probands), with known exposure status of both cotwins. To this end we derived formulae for two epidemiologic measures, as a function of prevalence of an exposure and genotype, and disease ri...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370110108
更新日期:1994-01-01 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::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::A range of study designs, using unrelated or family controls, were used to investigate the pattern of association with disease of single nucleotide polymorphisms (SNPs) within candidate gene 1 (simulated data). Strong evidence of disease association at the functional locus was detected using all study designs, and in ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.2001.21.s1.s415
更新日期:2001-01-01 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::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::Next-generation sequencing (NGS) has led to the study of rare genetic variants, which possibly explain the missing heritability for complex diseases. Most existing methods for rare variant (RV) association detection do not account for the common presence of sequencing errors in NGS data. The errors can largely affect ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21871
更新日期:2015-02-01 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::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::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::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::Standard linear regression is commonly used for genetic association studies of quantitative traits. This approach may not be appropriate if the trait, on its original or transformed scales, does not follow a normal distribution. A rank-based nonparametric approach that does not rely on any distributional assumptions c...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21723
更新日期:2013-05-01 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::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::In spite of the success of genome-wide association studies in finding many common variants associated with disease, these variants seem to explain only a small proportion of the estimated heritability. Data collection has turned toward exome and whole genome sequencing, but it is well known that single marker methods ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21746
更新日期:2013-09-01 00:00:00
abstract::The association between insulin-dependent diabetes mellitus (IDDM) and an allele of a restriction fragment length polymorphism (RFLP) 5' to the coding region of the insulin gene has raised the possibility that variation in the vicinity of the insulin gene confers susceptibility to IDDM. To test this hypothesis, the di...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370060113
更新日期:1989-01-01 00:00:00
abstract::A recently developed nonparametric method is a generalization of the transmission disequilibrium test across all alleles of a locus. This approach has been applied to Problem 2 of GAW10 and has been extended to explore the combined contribution of neighboring loci for chromosomes 1, 5, and 8. When applied to the chrom...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1997)14:6<857::AID-GEPI49>
更新日期:1997-01-01 00:00:00
abstract::Path analysis of family data has been widely applied to resolve genetic and environmental patterns of familial resemblance. A prevalent statistical approach in path analysis has been, first, to estimate the familial correlations and, second, by assuming these estimates to be independently distributed, define a likelih...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370010305
更新日期:1984-01-01 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 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::Sequencing studies using whole-genome or exome scans are still more expensive than genome-wide association studies on a per-subject basis. As a result, only a subset of subjects from a larger study will be selected for sequencing. To perform an agnostic investigation of the entire genome, subjects may be selected that...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21641
更新日期:2012-07-01 00:00:00
abstract::DNA methylation is an important epigenetic mechanism that has been linked to complex diseases and is of great interest to researchers as a potential link between genome, environment, and disease. As the scale of DNA methylation association studies approaches that of genome-wide association studies, issues such as popu...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21789
更新日期:2014-04-01 00:00:00
abstract::Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22288
更新日期:2020-07-01 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::It is generally accepted that cancer is caused by environmental and inherited factors but these are only partially identified. Family studies can be informative but they do not separate shared lifestyles and genes. We estimate familial risks for concordant cancers between spouses in common cancers of both sexes in ord...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/1098-2272(200102)20:2<247::AID-GEPI7>3.0.C
更新日期:2001-02-01 00:00:00
abstract::A genetic epidemiologic investigation of breast cancer involving 389 breast cancer pedigrees including information on 14,721 individuals from the Icelandic population-based cancer registry is presented. Probands were women born in or after 1920 and reported to have breast cancer in the cancer registry. The average age...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(200001)18:1<81::AID-GEPI6>
更新日期:2000-01-01 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::Testing association between a genetic marker and multiple-dependent traits is a challenging task when both binary and quantitative traits are involved. The inverted regression model is a convenient method, in which the traits are treated as predictors although the genetic marker is an ordinal response. It is known tha...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21738
更新日期:2013-09-01 00:00:00
abstract::Copper incorporation studies were performed on individuals from 58 pedigrees, comprising 140 sibships. As previously reported, there is considerable overlap between heterozygotes and normal homozygotes. Segregation analysis supports recessive inheritance of disease, with residual heritability for 64Cu uptake in cultur...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370030403
更新日期:1986-01-01 00:00:00