Epidemiologic and Genetic Approaches in the Study of Gene-Environment Interaction: an Overview of Available Methods

Andrieu, Nadine; Goldstein, Alisa M.

doi:10.1093/oxfordjournals.epirev.a017976

Cited by 101 publications

(66 citation statements)

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“…Assuming that the environmental exposure and genetic factors occur independently, analyses of case only studies offer better estimation of gene-environment interactions than those based on cases and controls. 20 If the independence assumption holds, assessment of geneenvironment interactions will not be subject to selection bias. 21 We did test this assumption on our data.…”

Section: Discussionmentioning

confidence: 99%

Fruit consumption reduces the effect of smoking on bladder cancer risk. The Belgian case control study on bladder cancer

Kellen

Zeegers

Paulussen

et al. 2006

Intl Journal of Cancer

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We have hypothesized that consumption of fruit and vegetables may be associated with reduced risk of bladder cancer and that this may interact with cigarette smoking and metabolic genetic polymorphisms. A population-based case-control study was performed in the Belgian province of Limburg among 200 cases and 385 controls. Logistic regression was performed to calculate odds ratios (ORs) for bladder cancer occurrence with corresponding 95% confidence intervals (95% CI). Effect modification by smoking was investigated. We also evaluated interaction between fruit intake and GSTM1, GSTT1, NAT2 and SULT1A1 amongst ''ever-smokers.'' Total vegetable intake was not significantly associated with the risk of bladder cancer (OR 1.15, 95% CI: 0.70-1.88 for the highest compared to the lowest tertile). However, total fruit intake was negatively associated with bladder cancer risk (OR 0.61, 95% CI 0.37-0.99 comparing the same tertiles). Among individuals with low daily fruit consumption, ever smokers had a highly increased risk of bladder cancer risk (OR: 4.23, 95% CI: 1.91-9.40). By increasing the daily fruit consumption, the risk of ''ever-smokers'' for developing bladder cancer decreased, however it remained significant (OR: 2.15; 95CI%: 1.15-4.05). No interaction was identified between the different genotypes and fruit consumption. We conclude that fruit consumption may decrease the effect of smoking on developing bladder cancer. Antioxidants, found in fruit, may protect against the damage caused by free radicals found in cigarette smoke. Metabolic polymorphisms appear not to modify this relation. ' 2005 Wiley-Liss, Inc.Key words: bladder cancer; fruit and vegetable intake; cigarette smoking; genetic polymorphisms An estimated 357,000 cases of bladder cancer occurred worldwide in 2002, making this the ninth most commonly occurring cancer for both sexes combined. There were 145,000 deaths, with population-based 5-year survival rates ranging from 40 to 80% depending on whether noninvasive lesions were included in the computation or not. Bladder cancer is relatively common in developed countries, where 63% of all incident cases are diagnosed.

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Section: Discussionmentioning

confidence: 99%

Fruit consumption reduces the effect of smoking on bladder cancer risk. The Belgian case control study on bladder cancer

Kellen

Zeegers

Paulussen

et al. 2006

Intl Journal of Cancer

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“…When data are collected on twins, a child's genetic risk for disorder can be estimated as a function of his or her co-twin's diagnostic status and the pair's zygosity (Andrieu & Goldstein, 1998;Kendler & Kessler, 1995;Ottman, 1994). These analyses are premised on the testable assumption that the disorder of interest is heritable, meaning that evidence is required to establish that genes partly account for individual differences in the disorder.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Nature × nurture: Genetic vulnerabilities interact with physical maltreatment to promote conduct problems

Jaffee

Caspi

Moffitt

et al. 2005

Develop. Psychopathol.

289

229

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Maltreatment places children at risk for psychiatric morbidity, especially conduct problems. However, not all maltreated children develop conduct problems. We tested whether the effect of physical maltreatment on risk for conduct problems was strongest among those who were at high genetic risk for these problems using data from the E-risk Study, a representative cohort of 1,116 5-year-old British twin pairs and their families. Children's conduct problems were ascertained via parent and teacher interviews. Physical maltreatment was ascertained via parent report. Children's genetic risk for conduct problems was estimated as a function of their co-twin's conduct disorder status and the pair's zygosity. The effect of maltreatment on risk for conduct problems was strongest among those at high genetic risk. The experience of maltreatment was associated with an increase of 2% in the probability of a conduct disorder diagnosis among children at low genetic risk for conduct disorder but an increase of 24% among children at high genetic risk. Prediction of behavioral pathology can attain greater accuracy if both pathogenic environments and genetic risk are ascertained. Certain genotypes may promote resistance to trauma. Physically maltreated children whose first-degree relatives engage in antisocial behavior warrant priority for therapeutic intervention.Maltreatment poses severe risks to children's health and development and is increasingly coming to the attention of primary care clinicians and other community professionals Sedlak & Broadhurst, 1996). A major consequence of maltreatment in early childhood is antisocial behavior (Dodge, Bates, & Pettit, 1990;Lansford, Dodge, Pettit, Bates, Crozier, & Kaplow, 2002;Smith & Thornberry, 1995;Widom, 1989;Widom & Maxfield, 2001). Such early-onset antisocial behavior is, in turn, associated with life-long and pervasive mental (Moffitt, Caspi, Harrington, & Milne, 2002), physical (Farrington, 1995), economic (Caspi, Wright, Moffitt, & Silva, 1998), and interpersonal problems that create an enormous public-health burden (Potter & Mercy, 1997).However, not all maltreated children develop conduct problems (Widom, 1997), and some maltreated children exhibit adaptive functioning (Cicchetti, Rogosch, Lynch, & Holt, 1993) that is still evident in adulthood (McGloin & Widom, 2001). Very little systematic evidence is available to explain why children show such marked variation in their response to maltreatment. Such variability would be observed if there were genetically influenced individual differences in susceptibility to environmental experiences like maltreatment, a Address correspondence and reprint requests to: Sara Jaffee, Department of Psychology, University of Pennsylvania, 3720 Walnut Street, Philadelphia, PA 19104; srjaffee@psych.upenn NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript concept referred to as "gene-environment interaction" (GxE; Kendler & Eaves, 1986;Rutter & Silberg, 2002). The GxE concept is familiar to clinicians as the "host-...

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“…Andre design og analysemetoder, som koblingsstudier og analyser av pasient-foreldre triader kan også brukes til å studere interaksjoner basert på beslektede prinsipper. Alle design har sine ulemper og fordeler (6,7,35). Clayton & KcKeigue har nylig hevdet at gen-gen og gen-miljøinteraksjoner ved komplekse sykdommer har begrenset vitenskapelig verdi, men at hvis man først skal undersøke slike interaksjoner med epidemiologiske design, så er case-kontroll designet å foretrekke (32).…”

Section: Diskusjonunclassified

“…Elston (2) og artiklene av Ellsworth & Manolio (3)(4)(5). For generelle oversikter over metoder for analyse av gen-miljøinteraksjoner med ulike design, se artiklene av Yang & Khoury og Andrieu & Goldstein (6,7). Denne artikkelen kan også vaere en nyttig introduksjon til logistisk regresjon for genetikere som har erfaring med tradisjonell tabellanalyse.…”

Section: Introduksjonunclassified

Introduksjon til analyse av gen-gen og gen-miljø interaksjoner i case-kontroll studier

Stene¹

2009

Nor J Epidemiol

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ENGLISH SUMMARYThe objective of this paper is to present a simple introduction to the analysis of gene-gene and geneenvironment interactions with the case-control design. The primary target group is epidemiologists with little or no experience in studies of molecular genetic markers. Fundamental concepts such as gene, allele, exposure and interaction are explained in the context of dose-response relationships. Principles for the socalled 'case-only' analysis are presented. Emphasis is put on the use of logistic regression analyses and how these are related to traditional analysis of contingency tables. INTRODUKSJONStudier av interaksjoner mellom gener og miljø eller mellom ulike gener er en viktig målsetning i genetisk epidemiologi (1). Hensikten med denne artikkelen er å presentere en enkel introduksjon til analyse av gen-gen og gen-miljø interaksjoner i case-kontroll studier samt såkalte case-only studier, med spesiell vekt på bruk av logistisk regresjon. HVA ER ET GEN OG HVA ER EKSPONERING?For folk flest er den nøyaktige betydningen av gen eller genotype uklar, og begrepene brukes ofte om ulike ting. En tradisjonell, men noe problematisk definisjon av et gen er "en sekvens DNA som koder for et protein". Med denne definisjonen korresponderer gen til locus (flertall: loci), som refererer til posisjon på kromosomet der genet finnes. Store deler av DNA koder ikke for proteiner, men kan allikevel inneholde viktig informasjon. Et locus kan derfor referere til en posisjon på kromosomet som ikke koder for proteiner og derfor strengt tatt ikke er 'gener'. Når det humane genom nå sies å vaere kartlagt betyr det at sekvensene er kjent i rimelig detalj, men det betyr ikke at man kjenner alle genenes posisjon eller funksjon. Mange gener finnes i to eller flere varianter som kalles alleler. Et locus hvor det finnes to eller flere ulike alleler i befolkningen kalles et polymorft sete. Enkelte foretrekker å bruke begrepet gen om et allel (1). Når man snakker om 'risikogener' menes som regel risikoalleler. Mennesket har to sett med såkalte homologe kromosomer, og dermed to utgaver av hvert 'gen'. Hvis det finnes flere varianter (alleler) av et gen i befolkningen, kan et individ ha null, ett eller to kopier av en gitt variant. Genotypen (med hensyn på

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Epidemiologic and Genetic Approaches in the Study of Gene-Environment Interaction: an Overview of Available Methods

Cited by 101 publications

References 50 publications

Fruit consumption reduces the effect of smoking on bladder cancer risk. The Belgian case control study on bladder cancer

Fruit consumption reduces the effect of smoking on bladder cancer risk. The Belgian case control study on bladder cancer

Nature × nurture: Genetic vulnerabilities interact with physical maltreatment to promote conduct problems

Introduksjon til analyse av gen-gen og gen-miljø interaksjoner i case-kontroll studier

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