title: Statistical issues in life course epidemiology.
abstract: There is growing recognition that the risk of many diseases in later life, such as type 2 diabetes or breast cancer, is affected by adult as well as early-life variables, including those operating prior to conception and during the prenatal period. Most of these risk factors are correlated because of common biologic and/or social pathways, while some are intrinsically ordered over time. The study of how they jointly influence later ("distal") disease outcomes is referred to as life course epidemiology. This area of research raises several issues relevant to the current debate on causal inference in epidemiology. The authors give a brief overview of the main analytical and practical problems and consider a range of modeling approaches, their differences determined by the degree with which associations present (or presumed) among the correlated explanatory variables are explicitly acknowledged. Standard multiple regression (i.e., conditional) models are compared with joint models where more than one outcome is specified. Issues arising from measurement error and missing data are addressed. Examples from two cohorts in the United Kingdom are used to illustrate alternative modeling strategies. The authors conclude that more than one analytical approach should be adopted to gain more insight into the underlying mechanisms.
authors.affiliation: Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom. bianca.destavola@lshtm.ac.uk
authors.forename: Bianca L
authors.initials: BL
authors.lastname: De Stavola
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nitsch
authors.forename: Isabel
authors.initials: I
authors.lastname: dos Santos Silva
authors.forename: Valerie
authors.initials: V
authors.lastname: McCormack
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hardy
authors.forename: Vera
authors.initials: V
authors.lastname: Mann
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Cole
authors.forename: Susan
authors.initials: S
authors.lastname: Morton
authors.forename: David A
authors.initials: DA
authors.lastname: Leon
mesh_terms: D015984:Causality; D003627:Data Interpretation, Statistical; D004812:Epidemiologic Methods; D006801:Humans; D008137:Longitudinal Studies; D015233:Models, Statistical; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors