Genetic Effects on Environmental Vulnerability to Disease

Much research has attempted to show direct linear relations between genes and disorder. However, scientists have been discouraged by inconsistent findings based on this simple gene-phenotype approach. The alternative approach is to incorporate information about the environment. A gene-environment interaction approach assumes that environmental pathogens cause disorder, whereas genes influence susceptibility to environmental pathogens. This book brings together contributions from experts from multiple disciplines who discuss: How epidemiological cohort studies can better integrate physiological (mechanistic) measures; How best to characterise subjects vulnerability versus resilience by moving beyond single genetic polymorphisms; How gene hunters can benefit from recruiting samples selected for known exposures; How environmental pathogens can be used as tools for gene hunting; How to deal with potential spurious (statistical) interactions, and How genes can help explain fundamental demographic properties of disorders (e.g. sex distribution, age effects).

Much research has attempted to show direct linear relations betweengenes and disorder. However, scientists have been discouraged byinconsistent findings based on this simple gene-phenotype approach.The alternative approach is to incorporate information about theenvironment. A gene-environment interaction approach assumes thatenvironmental pathogens cause disorder, whereas genes influencesusceptibility to environmental pathogens.This book brings together contributions from experts frommultiple disciplines who discuss:* How epidemiological cohort studies can better integratephysiological (mechanistic) measures;* How best to characterise subjects' vulnerability versusresilience by moving beyond single genetic polymorphisms;* How gene hunters can benefit from recruiting samples selectedfor known exposures;* How environmental pathogens can be used as tools for genehunting;* How to deal with potential spurious (statistical) interactionsand* How genes can help explain fundamental demographic propertiesof disorders (e.g. sex distribution, age effects).

1. Michael RutterIntroduction: whither gene-environment interactions?2. Rudolf UherGene-environment interaction: overcoming methodologicalchallengesDiscussion3. Marco Battaglia, Cecilia Marino, Michel Maziade, MassimoMolteni and Francesca D'AmatoGene-environment interaction and behavioural disorders: adevelopmental perspective based on endophenotypesDiscussion4. Naomi R. Wray, William L. Coventry, Michael R. JamesGrant W. Montgomery, Lindon J. Eaves and Nicholas G.MartinUse of monozygotic twins to investigate the relationship between5HTTLPR genotype, depression and stressful life events: anapplication of Item Response TheoryDiscussionAppendixGeneral discussion I5. Harold Snieder, Xiaoling Wang, Vasiliki Lagou, Brenda W.J. H. Penninx, Harriëtte Riese and Catharina A.HartmanRole of gene-stress interactions in gene-findingstudiesDiscussion6. Kenneth A. DodgePractice and public policy in the era of gene-environmentinteractionsDiscussion7. Kristi B. Adamo and FrédériqueTessonGene-environment interaction and the metabolicsyndromeDiscussionGeneral discussion II8. Stephen P. Robertson and RichiePoultonLongitudinal studies of gene-environment interaction incommon diseases--good value for money?Discussion9. Kee-Seng ChiaGene-environment interactions in breast cancerDiscussion10. Malak Kotb, Nourtan Abdeltawab, Ramy Aziz, SarahRowe, Robert W. Williams and Lu LuUnbiased forward genetics and systems biology approaches tounderstanding how gene-environment interactions work topredict susceptibility and outcomes of infectionsDiscussion11. Steven R. Kleeberger and Hye-YounChoGene-environment interactions in environmental lungdiseasesDiscussionGeneral discussion III12. Fernando D. MartinezGene-environment interaction in complex diseases: asthmaas an illustrative caseDiscussion13. Michael RutterConclusions: taking stock and looking aheadGlossaryIndex of contributorsSubject index