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 article extends demographic models that estimate relative mortality risks from changes in gene frequencies with age. The resulting demographic synthesis combines gene frequencies with data on mortality by genotype from cohort studies. The model was applied to data from Denmark, Finland, France, Italy, Sweden, and the United States. Near age 50, the 3/4 genotype is associated with a risk of death of 1.34 times that of the 3/3 (95% CI 1.18-1.67). The relative risk for 4/4 is the square of the relative risk for 3/4, 1.81. The 2/3 genotype is protective with a relative risk of 0.84 (0.68-0.93) near age 50. These relative risks move toward 1.0 at the oldest ages and APOE genotype is associated with little variation in mortality over age 100. There are no significant differences in the relative risks by sex. There is little evidence of differences within Europe in the effects of APOE. This approach can be generalized to combine data on genetic risk factors for disease from a wide variety of study designs and sample characteristics.
journal_name
Genet Epidemioljournal_title
Genetic epidemiologyauthors
Ewbank DCdoi
10.1002/gepi.0164subject
Has Abstractpub_date
2002-02-01 00:00:00pages
146-55issue
2eissn
0741-0395issn
1098-2272pii
10.1002/gepi.0164journal_volume
22pub_type
杂志文章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
abstract::To evaluate the risk of a disease associated with the joint effects of genetic susceptibility and environmental exposures, epidemiologic researchers often test for non-multiplicative gene-environment effects from case-control studies. In this article, we present a comparative study of four alternative tests for intera...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20337
更新日期:2008-11-01 00:00:00
abstract::In the last two decades, complex traits have become the main focus of genetic studies. The hypothesis that both rare and common variants are associated with complex traits is increasingly being discussed. Family-based association studies using relatively large pedigrees are suitable for both rare and common variant id...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21844
更新日期:2014-11-01 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 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::Jewish women have been reported to have a higher risk for familial breast cancer than non-Jewish women and to be more likely to carry mutations in breast cancer genes such as BRCA1. Because BRCA1 mutations also increase women's risk for ovarian cancer, we asked whether Jewish women are at higher risk for familial ovar...
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(1998)15:1<51::AID-GEPI4>3.
更新日期:1998-01-01 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
abstract::Recently, Liang et al. ([2001b] Genet. Epidemiol. 21:105-122) proposed a conditional approach to assess linkage evidence on the target region by incorporating linkage information from an unlinked (reference) region using allele shared IBD (identity-by-decent) from affected sib pairs. This is carried out by conditionin...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.10305
更新日期:2004-02-01 00:00:00
abstract::The present findings for familial Alzheimer's disease suggest a possible linkage to gene(s) on chromosome 21 for the early onset form and to chromosome 19 for the late onset. Since these results are not unequivocal, possible alternative hypotheses include the effect of genetic heterogeneity or of an oligogenic model o...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370100618
更新日期:1993-01-01 00:00:00
abstract::In this paper, we proposed a multipoint method to assess evidence of linkage to one region by incorporating linkage evidence from another region. This approach uses affected sib pairs in which the number of alleles shared identical by descent (IBD) is the primary statistic. This generalized estimating equation (GEE) a...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1021
更新日期:2001-09-01 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::The growing interest in detection of genetic effects for complex traits along with molecular revolution has stimulated many linkage studies. Multiple replication studies tend to produce different results. In such situations, rigorous meta-analysis methods can be useful for assessing the overall evidence for linkage. W...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1996)13:4<377::AID-GEPI6>3
更新日期:1996-01-01 00:00:00
abstract::Penalized regression methods offer an attractive alternative to single marker testing in genetic association analysis. Penalized regression methods shrink down to zero the coefficient of markers that have little apparent effect on the trait of interest, resulting in a parsimonious subset of what we hope are true perti...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20543
更新日期:2010-12-01 00:00:00
abstract::A major locus that determines levels of apolipoprotein B (apoB) was revealed by likelihood analysis on 331 members of 36 pedigrees. The major locus explained 43.2% of the observed variance, with the remainder attributed to random environmental factors. Estimated mean apoB levels (mg/dl) were 110.5 +/- 2.5, 141.9 +/- 4...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370040202
更新日期:1987-01-01 00:00:00
abstract::Methods for genetic risk prediction have been widely investigated in recent years. However, most available training data involves European samples, and it is currently unclear how to accurately predict disease risk in other populations. Previous studies have used either training data from European samples in large sam...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22083
更新日期:2017-12-01 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::Increased adiposity has repeatedly been identified as a major risk factor for a variety of chronic diseases. However, the question still remains whether the amount of adipose tissue itself is genetically mediated. To address this question, a segregation analysis, using maximum likelihood techniques as implemented in t...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370120505
更新日期:1995-01-01 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::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::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::By analyzing more next-generation sequencing data, researchers have affirmed that rare genetic variants are widespread among populations and likely play an important role in complex phenotypes. Recently, a handful of statistical models have been developed to analyze rare variant (RV) association in different study des...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21804
更新日期:2014-05-01 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::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::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::The availability of high-density haplotype data has motivated several fine-scale linkage disequilibrium mapping methods for locating disease-causing mutations. These methods identify loci around which haplotypes of case chromosomes exhibit greater similarity than do those of control chromosomes. A difficulty arising i...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20016
更新日期:2004-11-01 00:00:00
abstract::In genetic association studies, a single marker is often associated with multiple, correlated phenotypes (e.g., obesity and cardiovascular disease, or nicotine dependence and lung cancer). A pervasive question is then whether that marker exerts independent effects on all phenotypes. In this paper, we address this ques...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21660
更新日期:2012-09-01 00:00:00
abstract::We combined the five chromosome 18 bipolar affective disorder data sets provided by GAW10, totaling 185 families with 3,394 individuals, and performed analysis of differential parental transmission and chromosome 18 marker allele sharing in families with transmission through fathers vs those through mothers. Results i...
journal_title:Genetic epidemiology
pub_type: 临床试验,杂志文章
doi:10.1002/(SICI)1098-2272(1997)14:6<665::AID-GEPI19>
更新日期:1997-01-01 00:00:00
abstract::Four relative-pair methods for detecting genetic linkage were applied to familial Alzheimer's disease data. Results obtained using an extended Haseman-Elston test and a weighted rank pairwise correlation test, which both use information from all relative pairs, were consistent with previously published likelihood resu...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370100608
更新日期:1993-01-01 00:00:00
abstract::Genes, including those with transgenerational effects, work in concert with behavioral, environmental, and social factors via complex biological networks to determine human health. Understanding complex relationships between causal factors underlying human health is an essential step towards deciphering biological mec...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22363
更新日期:2020-09-30 00:00:00
abstract::The study of the genetic component of early-onset diseases requires investigation into parental genetic effects, particularly those mediated by the mother who can influence the offspring's risk of disease through the effects of her genes acting directly on the intrauterine milieu or indirectly through maternal-gene ch...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20602
更新日期:2011-09-01 00:00:00