Abstract:
:The 'Mendelian randomization' approach uses genotype as an instrumental variable to distinguish between causal and non-causal explanations of biomarker-disease associations. Classical methods for instrumental variable analysis are limited to linear or probit models without latent variables or missing data, rely on asymptotic approximations that are not valid for weak instruments and focus on estimation rather than hypothesis testing. We describe a Bayesian approach that overcomes these limitations, using the JAGS program to compute the log-likelihood ratio (lod score) between causal and non-causal explanations of a biomarker-disease association. To demonstrate the approach, we examined the relationship of plasma urate levels to metabolic syndrome in the ORCADES study of a Scottish population isolate, using genotype at six single-nucleotide polymorphisms in the urate transporter gene SLC2A9 as an instrumental variable. In models that allow for intra-individual variability in urate levels, the lod score favouring a non-causal over a causal explanation was 2.34. In models that do not allow for intra-individual variability, the weight of evidence against a causal explanation was weaker (lod score 1.38). We demonstrate the ability to test one of the key assumptions of instrumental variable analysis--that the effects of the instrument on outcome are mediated only through the intermediate variable--by constructing a test for residual effects of genotype on outcome, similar to the tests of 'overidentifying restrictions' developed for classical instrumental variable analysis. The Bayesian approach described here is flexible enough to deal with any instrumental variable problem, and does not rely on asymptotic approximations that may not be valid for weak instruments. The approach can easily be extended to combine information from different study designs. Statistical power calculations show that instrumental variable analysis with genetic instruments will typically require combining information from moderately large cohort and cross-sectional studies of biomarkers with information from very large genetic case-control studies.
journal_name
Int J Epidemioljournal_title
International journal of epidemiologyauthors
McKeigue PM,Campbell H,Wild S,Vitart V,Hayward C,Rudan I,Wright AF,Wilson JFdoi
10.1093/ije/dyp397subject
Has Abstractpub_date
2010-06-01 00:00:00pages
907-18issue
3eissn
0300-5771issn
1464-3685pii
dyp397journal_volume
39pub_type
杂志文章abstract:BACKGROUND:While prior studies of thyroid cancer incidence within Belarus have increased since the 1986 Chernobyl reactor accident, the magnitude of increase is not well quantified. METHODS:Using Belarussian national cancer registry data, trends in average annual age-adjusted thyroid cancer incidence rates were examin...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/dyh201
更新日期:2004-10-01 00:00:00
abstract::In view of the many changes in the approach to the detection and management of hypertension that have occurred, the paucity of current data on this subject in Israel limits the possibilities of making international comparisons or evaluating trends. This study contributes recent information on the occupationally-active...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/21.4.676
更新日期:1992-08-01 00:00:00
abstract:BACKGROUND:Recent economic growth in Papua New Guinea (PNG) would suggest that the country may be experiencing an epidemiological transition, characterized by a reduction in infectious diseases and a growing burden from non-communicable diseases (NCDs). However, data on cause-specific mortality in PNG are very sparse, ...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/dyz018
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND:Contact sports have high rates of injury. Protective equipment regulations are widely used as an intervention to reduce injury risk. The purpose of this study was to investigate the injury prevention effect of regulations governing protective equipment in two full-body contact sports. METHODS:Injury rates i...
journal_title:International journal of epidemiology
pub_type: 杂志文章,多中心研究
doi:10.1093/ije/31.3.587
更新日期:2002-06-01 00:00:00
abstract:BACKGROUND:Spot checks are becoming a popular method to assess hygiene behaviours; however, little is known about their repeatability or predictability. We evaluated the within-household repeatability of hygiene indices created from spot checks and their ability to predict incidence of diarrhoea in young Guatemalan chi...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/dyl165
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:Knowing the starting date of the BSE epidemic and its size at the very beginning is crucial to interpret the timing of the nvCJD cases and to forecast the nvCJD epidemic. The first cases occurred in 1985. The models devised by Anderson (back-calculation) and Dealler (age-period-cohort) led to an estimate of ...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/28.3.526
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND:Human immunodeficiency virus (HIV) and hepatitis B and C, viral infections with shared percutaneous, mucosal and perinatal routes of transmission, are responsible for serious morbidity and mortality globally. In Bangladesh there is a dearth of research on prevalence and risk factors for these diseases. This ...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/30.4.878
更新日期:2001-08-01 00:00:00
abstract:BACKGROUND:Accumulating evidence suggests that aspirin use may improve survival in cancer patients, however, for endometrial cancer, epidemiological evidence is limited and results are equivocal. In a nationwide cohort study, we examined the association between post-diagnostic low-dose aspirin use and endometrial cance...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/dyz253
更新日期:2020-02-01 00:00:00
abstract::A study was made in five rural districts of Kwara State, Nigeria to assess the possible use of 'leopard skin' (Ls) as a rapid diagnostic technique for estimating the endemicity of African onchocerciasis. The findings revealed that there is a positive association between the percentage of subjects with skin microfilari...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/16.4.590
更新日期:1987-12-01 00:00:00
abstract::In this study in 437 women born in 1948 selected from five European towns we show that several anthropometric measurements are consistently and significantly associated with a metabolic risk profile in premenopausal women of 38 years of age. Among the circumferences, breast and waist circumference were, after adjustme...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/19.2.303
更新日期:1990-06-01 00:00:00
abstract:BACKGROUND:Data from the Carolina Breast Cancer Study, a population-based, case-control study of breast cancer in African-American and white women residents of North Carolina, were evaluated to determine whether specific aspects of lactation are associated with a reduction in the risk of breast cancer. METHODS:Analyse...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/28.3.396
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND:This prospective study was performed in order to investigate the effect of baseline body mass index (BMI), BMI changes, baseline alcohol consumption, and changes in alcohol consumption on liver enzyme activity. METHODS:This study population consisted of 6846 male workers in a steel manufacturing company who...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/30.4.766
更新日期:2001-08-01 00:00:00
abstract:BACKGROUND:We undertook a systematic review and meta-analysis of perinatal variables in relation to testicular cancer risk, with a specific focus upon characteristics of the son. METHODS:Literature databases Scopus, EMBASE, PubMed and Web of Science were searched using highly sensitive search strategies. Of 5865 refer...
journal_title:International journal of epidemiology
pub_type: 杂志文章,meta分析,评审
doi:10.1093/ije/dyq120
更新日期:2010-12-01 00:00:00
abstract::A person to person outbreak of hepatitis A is described: 90 cases of hepatitis A occurred in a small town in Calabria, southern Italy; all cases were under 18 years of age with the highest age-specific incidence rate in the 6-10 year age group. Transmission was identified by tracing close contacts with other incubatin...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/15.1.108
更新日期:1986-03-01 00:00:00
abstract:BACKGROUND:Endometriosis has been associated with a higher risk of cutaneous melanoma, but the mechanisms underlying this association are unknown.Some constitutional factors known to influence melanoma risk have been associated with endometriosis in some retrospective studies. However, prospective data are scarce, and ...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/dyt235
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND:Epidemiology's role as the 'diagnostic' arm of public health has submitted epidemiological reasoning and practice to the crossfire of oppositional social values and demands. In Latin America, the visible signs of extreme social and political authoritarianism and inequity, as well as the growing unfairness of...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/dyn135
更新日期:2008-08-01 00:00:00
abstract:Background:The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia) and across birth coho...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/dyy081
更新日期:2018-08-01 00:00:00
abstract:BACKGROUND:Depression has been associated with chronic changes in the serum concentration of C-reactive protein (CRP) in observational studies, but it is unclear if this association is causal or is due to confounding and bias. Genetic studies are less subject to this type of error and offer an opportunity to investigat...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/dyp199
更新日期:2009-08-01 00:00:00
abstract::Many of the known or suspected risk factors of sex hormone-dependent cancers in women (low parity, delay in childbearing, etc) are typical features of modern reproductive behaviour. Within the USSR regional variations in principal reproductive characteristics and the incidence of breast and cervical cancers have been ...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/18.3.498
更新日期:1989-09-01 00:00:00
abstract:BACKGROUND:The impact and cost-effectiveness of couples' voluntary HIV counselling and testing (CVCT) has not been quantified in real-world settings. We quantify cost-per-HIV-infection averted by CVCT in Zambia from the donor's perspective. METHODS:From 2010 to 2016, CVCT was established in 73 Zambian government clini...
journal_title:International journal of epidemiology
pub_type: 杂志文章,多中心研究
doi:10.1093/ije/dyy203
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:In Western countries mortality dropped throughout the 20th century, but over and above the long-term falling trend, the death rate has oscillated over time. It has been postulated that these short-term oscillations may be related to changes in the economy. METHODS:To ascertain if these short-term oscillatio...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/dyi141
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:This study evaluated whether food insecurity and obesity were associated in a population sample in Trinidad. METHODS:A sample was drawn of 15 clusters of households, in north central Trinidad. Resident adults were enumerated. A questionnaire was administered including the short form Household Food Security ...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/dyg100
更新日期:2003-08-01 00:00:00
abstract::Coronary heart disease (CHD) is regarded as a disease of developed 'western' societies. Within developed societies, however, CHD is typically a disease of the less affluent socioeconomic classes. This has not always been the case. Forty years ago. CHD was reported to be more common among the upper social classes. In N...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/20.2.393
更新日期:1991-06-01 00:00:00
abstract::A case-control study of risk factors for child diarrhoeal disease was undertaken in a rural area of Nicaragua. Some 1229 children under the age of five were matched with an equal number of children of the same age presenting with other illnesses unrelated to water and sanitation. The main types of water supply were sa...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/20.2.527
更新日期:1991-06-01 00:00:00
abstract:BACKGROUND:Previous studies have shown that the serum level of sialic acid is associated positively with mortality from coronary disease and stroke. In this study its relation with carotid atherosclerosis was evaluated. METHODS:From the Atherosclerosis Risk in Communities (ARIC) Study, 323 cases with carotid intima-me...
journal_title:International journal of epidemiology
pub_type: 杂志文章,多中心研究
doi:10.1093/ije/25.5.953
更新日期:1996-10-01 00:00:00
abstract::The clustering of xerophthalmia in villages and in households was assessed among preschool children surveyed in the Lower Shire Valley, Malawi, and in Aceh province, Indonesia. Trachoma clustering was similarly assessed among the same children in Malawi. Trachoma clustered much more than xerophthalmia among villages a...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/17.4.865
更新日期:1988-12-01 00:00:00
abstract::Prospective data from the Matlab surveillance area in rural Bangladesh, 1974-1982, were used in this study to show that divorced and never-married adults (aged 15-44 years) had significantly higher mortality than their currently married peers with differences in disability status accounting for some of this excess ris...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/22.3.445
更新日期:1993-06-01 00:00:00
abstract::The association between social ties and survival was assessed using a stratified sample of 1060 elderly aged 60-89 years in the city of Tampere, Finland. During the 6.5-year follow-up, 240 men and 153 women died. Compared with married men, the death rate ratio among unmarried men was 1.7 and among widowers 1.2. The re...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/18.1.158
更新日期:1989-03-01 00:00:00
abstract:BACKGROUND:Trisomy 18 (Edwards' syndrome, T18) is the second most common trisomy in man. We describe 118 children with regular T18 who were ascertained clinically and cytogenetically in the Kuwait Medical Genetics Centre during 1980-1997. METHODS:Ascertainment of T18 cases was performed shortly after birth. Chromosoma...
journal_title:International journal of epidemiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/ije/28.4.711
更新日期:1999-08-01 00:00:00
abstract::Mortality among male employees was studied in a chromium chemical production plant, part of which was rebuilt in 1950-51 and the remainder in 1960, to reduce exposure to chromium bearing dusts. Of 2 101 employees initially employed between 1945 and 1974 and having worked at least 90 days, the vital status of 88% was a...
journal_title:International journal of epidemiology
pub_type: 杂志文章
doi:10.1093/ije/8.4.365
更新日期:1979-12-01 00:00:00