SEARCH · PubMed Health

Results for “case-only”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1999

Detection of gene-environment interaction by case-only studies.

BACKGROUND: The detection of gene-environment interaction can provide important clues not only for resolving biological mechanisms underlying diseases, but also for disease prevention. The newly introduced case-only study was compared with traditional case-control study in terms of statistical power to detect significant gene-environment interaction. METHODS: Odds ratios for interaction were calculated in the framework of case-control study and case-only study separately, by an unconditional logistic model. Hypothetical data with 200 cases and 200 or 400 controls and real published data derived from four cancer case-control studies of genotype and smoking were used for the comparisons. RESULTS: Although odds ratio estimates for interaction were the same, 95% confidence intervals were narrower in case-only studies than in case-control studies. Similarly, there were no substantial differences in point estimates for interaction in four real cancer case-control studies between the two study designs, but the confidence intervals were narrower with the case-only study. CONCLUSIONS: Although the case-only study does not provide odds ratios for exposure or genotype alone, it is very useful for the detection of interaction, especially for screening purposes.

Case-Control Studies↗

PubMed1997

Sample size requirements in case-only designs to detect gene-environment interaction.

With advances in molecular genetic technology, more studies will examine gene-environment interaction in disease etiology. If the primary purpose of the study is to estimate the effect of gene-environment interaction in disease etiology, one can do so without employing controls. The case-only design has been promoted as an efficient and valid method for screening for gene-environment interaction. The authors derive a method for estimating sample size requirements, present sample size estimates, and compare minimum sample size requirements to detect gene-environment interaction in case-only studies with case-control studies. Assuming independence between exposure and genotype in the population, the authors believe that the case-only design is more efficient than a case-control design in detecting gene-environment interaction. They also illustrate a method to estimate sample size when information on marginal effects (relative risk) of exposure and genotype is available from previous studies.

Case-Control Studies↗

PubMed1999

Potential misinterpretation of the case-only study to assess gene-environment interaction.

Novel epidemiologic study designs are often required to assess gene-environment interaction. A design using only cases, without controls, is one of several approaches that have been proposed as more efficient alternatives to the typical random sampling of cases and controls. However, it has not been pointed out that a case-only analysis estimates a different interaction parameter than does a traditional case-control analysis: The latter typically estimates departure from multiplicative population odds or rate ratios, depending on the method of control selection, while the former estimates departure from multiplicative risk ratios if genotype and environmental exposure are not associated in the population. These parameters are approximately equal if the disease risk is small at all levels of the study variables. The authors quantify the impact of allowing for higher disease risk among gene carriers, a relevant situation when the gene under study is highly penetrant. Their findings show that the cross-product ratio computed from case-only data may be substantially smaller than the odds ratio computed from case-control data and may therefore underestimate either the population odds or the rate ratio. Thus, to avoid misinterpretation of interaction parameters estimated from case-only data, the definition of multiplicative interaction should be made explicit.

Case-Control Studies↗

PubMed1999

Case-only design to measure gene-gene interaction.

The case-only design is an efficient and valid approach to screening for gene-environment interaction under the assumption of the independence between exposure and genotype in the population. In this paper, we show that the case-only design is also a valid and efficient approach to measuring gene-gene interaction under the assumption that the frequencies of genes are independent in the population. Just as the case-only design requires fewer cases than the case-control design to measure gene-environment interaction, it also requires fewer cases to measure gene-gene interactions.

Epidemiologic Studies↗

PubMed2000

[Oral contraception and genetic factors in breast cancer: characteristics and limits of case-only studies].

The analysis of the interaction between environmental and genetic factors is a matter of increasing interest in cancerology. More particularly the discovery of the BRCAx family and the high cumulated incidence of familial breast cancers related to mutations of these proteins raised the issue of the differential effect of long term and/or early exposure to oral contraceptives in the presence of these mutations. The classical case-control design assumes the presence of a control group, which can be sometimes difficult to obtain from both the technical and ethical points of view. Case-only or case-case studies, which are based only on series of cases, making them apparently attractive, have been proposed to analyze more specifically the interaction term. The aim of the present paper is to review and discuss the methodological basis and main assumptions of the case-only design, and their applicability to breast cancer studies. The measure of the interaction between an environmental factor and a susceptibility genetic factor differs in an important aspect from the measure of the association between an environmental factor and a acquired tumoral genetic factor; this aspect is reminded.

Breast Neoplasms↗

PubMed1999

A unified approach to the analysis of case-distribution (case-only) studies.

A number of new study designs have appeared in which the exposure distribution of a case series is compared to an exposure distribution representing a complete theoretical population or distribution. These designs include the case-genotype study, the case-cross-over study, and the case-specular study. This paper describes a unified likelihood-based approach to the analysis of such studies, and discusses extensions of these methods when a control group is available. The approach clarifies certain assumptions implicit in the methods, and helps contrast these assumptions to those underlying ordinary case-control studies. There are several reasons to expect discrepancies between ordinary case-control estimates and case-distribution estimates; for example, case-distribution estimates can be more sensitive to exposure misclassification. Some discrepancies are illustrated in an application to case-specular data on wire codes and childhood cancer.

Case-Control Studies↗

PubMed1994

Non-hierarchical logistic models and case-only designs for assessing susceptibility in population-based case-control studies.

This article describes how genetic components of disease susceptibility can be evaluated in case-control studies, where cases and controls are sampled independently from the population at large. Subjects are assumed unrelated, in contrast to studies of familial aggregation and linkage. The logistic model can be used to test collapsibility over phenotypes or genotypes, and to estimate interactions between environmental and genetic factors. Such interactions provide an example of a context where non-hierarchical models make sense biologically. Also, if the exposure and genetic categories occur independently and the disease is rare, then analyses based only on cases are valid, and offer better precision for estimating gene-environment interactions than those based on the full data.

Biomarkers↗

PubMed2000

Minor events and the risk of deep venous thrombosis.

BACKGROUND: Deep venous thrombosis is a common disease, with genetic and acquired risk factors. Many patients have a history of minor events (short periods of immobilisation such as prolonged travel, short illness, minor surgery or injuries) before onset of venous thrombosis. However, the role of these minor events has received little formal study. Also, we do not know how minor events might interact with the presence of genetic prothrombotic defects (factor V Leiden mutation, factor II mutation, protein C, S and antithrombin deficiency). PATIENTS AND METHODS: On the basis of case-control data from a thrombosis service in the Netherlands, we added a follow-up period for a case-cross-over analysis of minor events as risk factors, and a case-only analysis for the interaction with factor V Leiden. A total of 187 patients with first, objectively diagnosed venous thrombosis of the legs, aged 15-70, without underlying malignancies and without major acquired risk factors entered the study. For the analysis of minor events in the case-cross-over analysis, we used a matched odds ratio; in the case-only analysis, we used the multiplicative synergy index. RESULTS: In 32.6% of the 187 patients with deep venous thrombosis who did not have major acquired risk factors, minor events were the only external risk factors. Minor events increased the risk of thrombosis about 3-fold, as estimated in the case-cross-over analysis (odds ratio 2.9, 95% confidence interval 1.5-5.4). The synergy index between minor events and factor V Leiden mutation in the case-only analysis was 0.7 (95% confidence interval 0.3-1.5). Therefore, persons with factor V Leiden mutation who experience a minor event will have an estimated risk increase of about 17-fold, which exceeds the sum of the individual risk factors. CONCLUSIONS: Minor events are likely to play an important role in the development of deep venous thrombosis, especially in the presence of genetic prothrombotic conditions.

Adolescent↗

PubMed1996

Nontraditional epidemiologic approaches in the analysis of gene-environment interaction: case-control studies with no controls!

Although case-control studies are suitable for assessing gene-environment interactions, choosing appropriate control subjects is a valid concern in these studies. The authors review three nontraditional study designs that do not include a control group: 1) the case-only study, 2) the case-parental control study, and 3) the affected relative-pair method. In case-only studies, one can examine the association between an exposure and a genotype among case subjects only. Odds ratios are interpreted as a synergy index on a multiplicative scale, with independence assumed between the exposure and the genotype. In case-parental control studies, one can compare the genotypic distribution of case subjects with the expected distribution based on parental genotypes when there is no association between genotype and disease; the effect of a genotype can be stratified according to case subjects' exposure status. In affected relative-pair studies, the distribution of alleles identical by descent between pairs of affected relatives is compared with the expected distribution based on the absence of genetic linkage between the locus and the disease; the analysis can be stratified according to exposure status. Some or all of these methods have certain limitations, including linkage disequilibrium, confounding, assumptions of Mendelian transmission, an inability to measure exposure effects directly, and the use of a multiplicative scale to test for interaction. Nevertheless, they provide important tools to assess gene-environment interaction in disease etiology.

Case-Control Studies↗

PubMed1997

Designing and analysing case-control studies to exploit independence of genotype and exposure.

Genetic susceptibility and environmental exposures play a synergistic role in the aetiology of many diseases. We consider a case-control study of a rare disease in relation to a categorical exposure and a genetic factor under the assumption that the genotype and the exposure occur independently in the population under study. Using a logistic model for risk, we describe maximum likelihood methods based on log-linear models that explicitly impose the independence assumption, something the usual logistic regression analyses cannot do. The estimator of the genotype-exposure interaction effect depends only on data from cases. Estimators for genotype and for exposure effects depend also no data from controls, but only through their respective marginal totals. All three estimators have smaller variance than they would were independence not enforced. These results have important implications for design: (i) Case-only studies can efficiently estimate gene-by-environment interactions. (ii) Studies where controls are genotyped anonymously can estimate genotype, exposure, and interaction effects as efficiently as designs where genotype and exposure data are linked. This feature addresses a growing concern of human subjects review boards. (iii) Exposure and interaction effects, but not genotype effects, can be estimated from studies where genetic information is only collected from cases (although one can recover the genotype effect if external gene prevalence data exist). Such designs have the compensatory benefit that the response rate (hence, validity) is higher when controls are not subjected to intrusive tissue sampling. However, the independence assumption can be checked only with linked genotype and exposure data for some controls. We illustrate the methods by applying them to recent study of cleft palate in relation to maternal cigarette smoking and to a variant of the transforming growth factor alpha gene in the child.

Case-Control Studies↗

PubMed2026

Trio-based GWAS reveals loci associated with different forms of isolated cleft lip.

Orofacial clefts (OFCs) are the most common craniofacial birth defect and comprise a diverse group of traits with complex and heterogeneous etiologies. Genetic studies of OFCs typically approach this diversity by stratifying cases into broad diagnostic classes, including cleft lip (CL), cleft palate (CP), and cleft lip with palate (CLP). Although this strategy has yielded important insights into OFC risk, it ignores the phenotypic heterogeneity within each subtype. CL exhibits marked phenotypic variability, involving differences in alveolar involvement, laterality, and sidedness that may reflect distinct etiologies. Given this phenotypic diversity within CL, we assembled a multi-ancestry cohort of 837 nonsyndromic CL case-parent trios with whole-genome sequencing and detailed phenotyping. We performed genome-wide association scans (GWAS) via transmission disequilibrium tests for CL overall and for 14 CL subtypes defined by involvement of the alveolus (with and without), laterality (uni- and bilateral), and sidedness (left and right). We identified four genome-wide significant loci. Two loci, IRF6 and 8q24.21, were both detected in the overall CL GWAS. PLCB1/PLCB4 and MAFB were detected in GWASs of alveolar cleft involvement and CL left sidedness, respectively. These subtype-specific associations were followed by case-only comparisons that reflect the presence or absence of alveolus cleft or left-sided bias of CL to confirm the specificity of the association signal to the particular subtype. Our results provide evidence of within-class CL subtype-specific genetic links for loci previously discussed in the context of primary OFC classes and demonstrate the value of granular OFC subtype characterization to capture trait-specific associations.

Alveolus Cleft↗

PubMed2000

Parental smoking, CYP1A1 genetic polymorphisms and childhood leukemia (Québec, Canada).

OBJECTIVE: To evaluate the effect of parental smoking on childhood acute lymphoblastic leukemia and to determine if it is modified by child genetic polymorphisms. METHODS: We carried out a case-control study in Quebec, Canada, including 491 incident cases aged 0-9 years and as many healthy controls matched on age and sex. Each parent was interviewed separately with respect to smoking habits during and after pregnancy. In addition, we carried out a case-only substudy with 158 cases classified according to presence or absence of the alleles *2A, *2B, and *4 in the CYP1A1 gene. RESULTS: There were small risk increases with maternal smoking during the later trimesters. Interaction odds ratios were increased (although often not significantly) for the CYP1A1*4 allele at high levels of maternal smoking in the last trimesters and at low level of paternal postnatal smoking, and decreased for the CYP1A1*2B allele. The latter appeared to confer a protective advantage at low levels for maternal prenatal smoking and at high levels for paternal postnatal smoking. CONCLUSIONS: Reported smoking habits showed no association with leukemia; risks for genetic polymorphisms lacked precision but indicated that the effect of parental smoking could be modified by variant alleles in the CYP1A1 gene.

Alleles↗

PubMed1995

[Legal problems in obstetrics. On the "liability of the expert witness"].

There has been a depressing increase in claims for damages and associated civil code and legal code proceedings in medicine in general (as the term "defensive medicine" illustrates) that exercises considerable influence on medical activities in obstetrics, not always to the benefit of the patients. In what manner and to what extent the expert can and must influence legal decisions, is demonstrated by means of a few examples such as management of parturition in case of breech presentation, causal assessment of psychomotoric retardation in postnatal life and the management of dystocia in shoulder presentation. If judges and attorneys are blamed-as is often the case-one should always also consider the significance of expertising activities. Typical errors occurring during expert assessment are pointed out. This shows the high degree of responsibility that has to be shouldered by the expert when he advises judges and/or attorneys. Expertising activities should be directed to a greater measure than in recent years, at delivering expertises restricted to the factual situation without involving emotions. This would at the same time reduce the influence of judges, attorneys and lawyers on our medical activities, an influence that has recently been much deplored.

Birth Weight↗

PubMed2026

Frequency and clinical features of germline pathogenic variants in sarcoma: a case-control study.

BACKGROUND: Germline multigene panel testing is not yet integrated into standard care for patients with sarcoma. This study aimed to assess the frequency and distribution of germline pathogenic variants in patients with sarcoma compared with cancer-free controls and identify differences between patients with and without germline pathogenic variants. METHODS: This retrospective cohort included 488 sarcoma patients and 2440 cancer-free controls matched 1:5 by age, sex, and ethnicity. Multigene panel testing was performed between 2016 and 2024 at a single germline testing laboratory. The frequency of germline pathogenic variants in selected genes was compared using Fisher exact test with odds ratios (ORs) and 95% confidence intervals. Additionally, within the case-only cohort, clinical characteristics were evaluated to assess associations with the presence of germline pathogenic variants in any gene. RESULTS: Among 488 patients with sarcoma, 67.8% (n = 331) were female, with a median age at sarcoma diagnosis of 47 years (range = 0.5-87.5 years). Cases had a higher frequency of germline pathogenic variants compared with controls (26.2% vs 10.5%; OR = 3.05, P < .001). We observed a higher frequency of germline pathogenic variants in TP53, BRCA2, CHEK2, NF1, SDHA, BRIP1, POT1, RB1, and CDH1 among patients with sarcoma compared with controls. Age at sarcoma diagnosis did not differ between groups. CONCLUSIONS: This study confirms the high detection rate of germline pathogenic variants in patients with sarcoma and describes several associated genes. These findings indicate that age at sarcoma diagnosis may not reliably predict germline pathogenic variants. Expanding germline testing for patients with sarcoma would enhance personalized treatment strategies and familial risk assessment.

Humans↗

PubMed2025

A comprehensive evaluation of candidate genetic polymorphisms in a large histologically characterized MASLD cohort using a novel framework.

BACKGROUND: There is a substantial heritable component to metabolic dysfunction-associated steatotic liver disease (MASLD), and several genetic variants that promote MASLD development or associate with its severity have been reported. These associations vary in terms of their effect size and degree of replication. METHODS: We developed a framework to classify previously identified MASLD genetic polymorphisms into 4 tiers based on effect size and extent of replication in the literature. We tested the association between "tier 1" single-nucleotide polymorphisms (OR ≥1.5, replicated in >2 independent studies) and biopsy measures of MASLD severity in a large, well-characterized histologic cohort of MASLD patients (n=3094). RESULTS: Across 19 "tier 1" variants reflecting 11 genetic loci, only those in the PNPLA3-SAMM50-PARVB locus showed significant associations with biopsy-proven fibrosis severity and NAFLD activity score; the highest risk was for the rs738409 p.I148M variant in PNPLA3. A genetic risk score based on "tier 1" variants, as well as a previously developed genetic risk score based on variants in PNPLA3, TM6SF2, and HSD17B13, were both associated with fibrosis and NAFLD activity score, but these results were driven entirely by PNPLA3 rs738409. CONCLUSIONS: Our study provides a framework to prioritize evaluation of genetic polymorphisms for future replication efforts and demonstrates that in a large case-only cohort, histologic severity of MASLD is only robustly associated with the presence of variation in PNPLA3 among known candidate genes. These findings may have implications for patient risk stratification based on the presence of PNPLA3 rs738409.

Humans↗

PubMed2025

Patient stratification by genetic risk in Alzheimer's disease is only effective in the presence of phenotypic heterogeneity.

Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science. In four cohorts (n = 7241), we performed genome-wide association studies (GWAS) and Mendelian randomization (MR) to discover novel targets associated with progression and assess causal relationships. We tested opportunities for patient stratification by deriving polygenic risk scores (PRS) for AD risk and severity and tested the value of these scores in predicting progression. Genome-wide association studies identified no loci associated with progression at genome-wide significance (α = 5×10-8); MR analyses provided no significant evidence of an association between cognitive decline in AD patients and protein levels in brain, cerebrospinal fluid (CSF), and plasma. Polygenic risk scores for AD risk did not reliably stratify fast from slow progressors; however, a deeper investigation found that APOE ε4 status predicts amyloid-β and tau positive versus negative patients (odds ratio for an additional APOE ε4 allele = 5.78 [95% confidence interval: 3.76-8.89], P<0.001) when restricting to a subset of patients with available CSF biomarker data. These results provided no evidence for large-effect, common-variant loci involved in the rate of memory decline, suggesting that patient stratification based on common genetic risk factors for progression may have limited utility. Where clinically relevant biomarkers suggest diagnostic heterogeneity, there is evidence that a priori identified genetic risk factors may have value in patient stratification. Mendelian randomization was less tractable due to the lack of large-effect loci, and future analyses with increased samples sizes are needed to replicate and validate our results.

Alzheimer Disease↗

PubMed1999

Risk of childhood leukemia associated with exposure to pesticides and with gene polymorphisms.

We conducted a population-based case-control study of childhood acute lymphoblastic leukemia (ALL) to evaluate the risk posed by reported exposure to pesticides used in and around the home. We compared 491 cases 0-9 years of age to as many controls. We also conducted a case-only study on a subsample of 123 cases to evaluate gene-environment interaction between child genotype and maternal exposure during pregnancy as well as child exposure after birth. We used the polymerase chain reaction (PCR) approach to analyze polymorphisms in CYP1A1, CYP2D6, GSTT1, and GSTM1 genes, which encode enzymes involved in carcinogen metabolism. Indoor use of some insecticides by the owners and pesticide use in the garden and on interior plants, in particular frequent prenatal use, was associated with increased risks up to severalfold in magnitude. Interaction odds ratios were increased among carriers of the CYP1A1m1 and CYP1a1m2 mutations when mother during pregnancy or the child had been exposed to certain indoor insecticides. No such effects were observed in the presence of other tested polymorphisms.

Case-Control Studies↗

PubMed1997

[Alcohol, street drugs and therapeutic drugs in street traffic].

While the rigorous prosecution of drunken drivers in Germany has resulted in a decrease in alcohol related accidents since the 1990s, the relevant risks of legal or illegal drugs are still receiving too little attention, and legal proceedings are rare. A study carried out at the beginning of the 1990s and data from a roadside survey in two distinct regions of Germany (Franken and Thüringen) show that the effect of illegal drugs and medications is almost equally as important as those of alcohol. A new bill proposes a general ban on driving under the influence of drugs, both legal and illegal. A major problem, however, is the need to show drug/medication misuse and recognize the specific symptoms in the individual case-only then successful use can be made of already existing legal remedies.

Accidents, Traffic↗