Previous research has explored the links between later-life health and various childhood conditions, such as socioeconomic status, adverse childhood experiences, and trauma. However, numerous other childhood life circumstances and their relative significance have yet to be examined. This study investigated the association between childhood life circumstance factors and chronic diseases among middle-aged and elderly individuals.Participants were sourced from the China Health and Retirement Longitudinal Study (CHARLS), a nationwide survey spanning 2011 to 2020. This study utilized 42,181 observations from 16,681 middle-aged and older adults, averaging around 60 years of age. Females constituted 58.12% of the sample. We examined 50 life circumstance factors across six domains: childhood socioeconomic status, wartime experiences during childhood, childhood health, childhood trauma, childhood relationships, and parental health. Data on these factors were derived from CHARLS's 2014 life history survey, alongside chronic disease and demographic information obtained from baseline surveys in 2011 and subsequent follow-ups through 2020. Chronic disease status relied on self-reported physician diagnoses. Logistic regression was employed to investigate the association between childhood life circumstance factors and adult chronic disease status. The study utilized the Least Absolute Shrinkage and Selection Operator (LASSO) method to identify significant factors, followed by quantile g-computation (QGC) to assess their relative importance. Additionally, the K-Means cluster method was used to categorize individuals based on similar childhood life circumstances, exploring susceptibility to chronic diseases within these subpopulations using logistic regression, LASSO, and QGC analyses.Of the 42,181 observations from 16,681 middle-aged and older adults, over 71.36% reported chronic diseases. Out of the 50 childhood life circumstance factors examined, 17 were found to have a statistically significant positive association with chronic diseases. LASSO identified 20 factors with non-zero coefficients, with parental deformity emerging as the most significant contributor to chronic disease development, accounting for 23.50% of the variance according to QGC. Four distinct subpopulations were identified, with Subpopulation 1 representing the most disadvantaged group.Our findings underscored the enduring impact of childhood life circumstances on chronic disease development later in life, with parental deformity identified as the most influential childhood factor. The most disadvantaged subpopulation includes individuals with higher prevalence of health problems during childhood, born during wartime, and with parents having a history of health issues.Copyright © 2024 Elsevier Ltd. All rights reserved.