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Early conditions, delayed adult effects and morbidity, disability and mortality in modern human populations

Periodic Reporting for period 1 - ECHO (Early conditions, delayed adult effects and morbidity, disability and mortality in modern human populations)

Reporting period: 2019-03-01 to 2020-08-31

ECHO aims to reformulate and generalize standard theories of human health and mortality. It proposes to empirically test hypotheses issued in disparate disciplines including developmental biology, genetics, population health and evolutionary biology, to better understand the evolution of adult human illness, disability and mortality. Over the past two decades there has been massive growth of research on the nature of delayed adult effects of conditions experienced in early life. This field of research is known as the Developmental Origins of Adult Health and Disease (DOHaD). Increasing empirical evidence suggests that some of the mechanisms that are implicated are epigenetic and constitute an evolved adaptation selected over thousands of years to improve fitness in changing landscapes. Of central importance are epigenetic and other partially (or fully) heritable mechanisms that enable organisms to respond to environmental by altering phenotypes. These mechanisms are the main candidate mediators that link pre-pregnancy, embryonic, fetal and early childhood exposures and adult chronic illnesses and conditions. Identifying these mechanisms will transform our understanding of past, current and future human illnesses and help bridge disciplines such as population health, epigenetics, and developmental and evolutionary biology. The project will contribute to this nascent area of study by (a) proposing new formal demographic models of health, disability and mortality; (b) empirically testing DOHaD predictions with data on human populations; (c) formulating and implementing a microsimulation model that includes representation of stochastic molecular processes, early and late exposures, and individual behaviors to forecast the two most prevalent conditions in contemporaneous human populations, obesity and Type 2 Diabetes (and associated comorbidities), and (d) assessing the adult health, disability, mortality and economic implications of future evolution of obesity and T2D.
A. Sub-project I: early childhood adversity and adult conditions

A. 1. Completed work on the effects of the 1918 flu on the nutritional status of survivors (forthcoming paper in PLOS);

A. 2. Completed analysis of relations between past mortality regimes and physical growth of cohorts with application of Waaler surfaces and a comparison between adults living in high and low to middle income countries. Paper submitted for publication to Population and Development Review

A.3. Completed initial design and implementation of a microsimulation model that forecast adult prevalence of diseases as a function of prevalence of adverse early conditions. Paper under review in Population Studies

A.4. Completed assessment of trends in healthy life expectancy among Spanish cohorts between 2012 and 2017. Identified deviant roles of birth cohorts who experienced the Spanish Civil War as infants and children. Paper under review

B. Subproject II: Formal models of relations between early conditions and adult health

B.1. Completed analysis of historic and simulated data sets cohorts born between 1900 and 1980 to identify cohort mortality patterns. Utilized state of the art APC models and proved that the most used among these models fail to produce correct results. Draft paper in progress.

B.2. Ongoing task of managing four large data sets (MHAS, PREHCO, SABEColombia, CRELES) to estimate multistate models identifying the effects of adverse early experiences on adult health transitions

C. Subproject III: effects of early exposure to social mobility and adult health and mortality

C.1. Completed work analyzing data from USA counties linking county-based social mobility indicators and adult health conditions and health related behaviors of individuals who lived in those counties as children. This project uses USA data from PSID and NLSY. Draft paper in progress.

D. Subproject IV: Developmental origins of adult health and diseases and the health of migrant children

D.1. Created a data base consisting of research studies reporting a relation between child obesity and metabolic dysfunction among children of migrants from low income countries who live in high income countries.

D.2. Ongoing task: performing metaanalysis on the data base referred to in D.1. above

D.3. Draft paper inprogress

E. Subproject V: Early adversity, genetic risks and G x E interactions

E.1. We are investigating gene x environment interactions in relation to genetic predisposition to obesity and T2D. We find that excess risks of both obesity and T2D among individuals who have higher genetic propensity to the phenotypes is higher among those who (a) grew up in poorer environments and (b) experience obesogenic environments as adults.

F. Subproject VI: physiological clocks and the assessment of biological age

F.1.We formulate and develop a model to estimate biological age (BA) from chronological age (CA) and biomarkers routinely collected in health surveys. The models is bases on a non lineal relation between a latent (unmeasured) construct (BA) and measured covariates. We use structural equation models, estimate basic parameters and then use the difference between predicted BA and CA to assess its effects on health conditions and mortality.
Paper submitted PAA meeting 2021

G. Subproject VII: Waaler surfaces

G.1 We utilize Waaler surfaces to show that the evolution of human growth follows different paths that depend on the nature of the secular mortality decline that a population experiences. Paper submitted to PAA meeting 2021
During the first 18 months of the project we succeeded in producing three contributions

a. Formulated a new model to estimate biological age from information routinely collected in elderly surveys. The model produces an indicator analogous to an epigenetic clocks except that instead of being based on measures of CpG methylation density, it relies on more conventional biomarkers.

b. Identified a relation between Type II Diabetes and obesity that has not been referred to in the literature. Using data from HRS we demonstrate that most of the increased risk of T2D among those who are obese is associated with the physiological effects of obesity and not on the overlap of genetic variants responsible for both obesity and T2D. This finding may have important repercussions since it suggests different strategy to prevent T2D among overweight or obese people.

c. Completed a paper (forthcoming in PLOS ONE) where we demonstrate for the first time (to our knowledge) that the 1918 Flu pandemic had long term consequences for the nutritional status of survivors.