Advantageous early-life environments cushion the genetic risk for ischemic heart disease

• 成果类型: Article
• 署名作者: Baker, Samuel; Biroli, Pietro; van Kippersluis, Hans; von Hinke, Stephanie
• 署名单位: University of Bristol; University of Bologna; Erasmus University Rotterdam; Erasmus University Rotterdam - Excl Erasmus MC; University of London; London School Economics & Political Science
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11856
• DOI: 10.1073/pnas.2314056121
• 发表日期: 2024-07-02
• 关键词: developmental origins; association analysis; HEALTH; loci; stratification; investments; endowments; allocation; families

摘要

In one of the first papers on the impact of early -life conditions on individuals' health in older age, Barker and Osmond [ Lancet , 327, 1077-1081 (1986)] show a strong positive relationship between infant mortality rates in the 1920s and ischemic heart disease in the 1970s. We merge historical data on infant mortality rates to 370,000 individual records in the UK Biobank using information on local area and year of birth. We replicate the association between the early -life infant mortality rate and laterlife ischemic heart disease in our sample. We then go beyond Barker, by showing considerable genetic heterogeneity in this association that is robust to within -area as well as within -family analyses. We find no association between the polygenic index and heart disease in areas with the lowest infant mortality rates, but a strong positive relationship in areas characterized by high infant mortality. These findings suggest that advantageous environments can cushion one's genetic disease risk.