Robel Alemu

The introduction of salt iodization is associated with improved health and socioeconomic outcomes, but is not yet universally adopted and is not always sustained. Using a quasi-experimental event study with difference-in-differences over space and time, we quantify the impacts of iodine deficiency in utero and during infancy on childhood mortality and later academic achievement in Ethiopia, comparing cohorts born just before and after the May 1998 border closure that interrupted access to iodized salt. Rural children with fewer months of early-life exposure to iodized salt scored lower on standardized secondary-school exams, especially in districts with low environmental iodine, with excess deaths emerging in infancy and persisting through early childhood. These findings reveal the long-term benefits of salt iodization for health and education, especially for people with low intake of iodine from environmental sources.

The introduction of salt iodization is associated with improved health and socioeconomic outcomes, but is not yet universally adopted and not always sustained. Using a quasi-experimental event study with difference-in-differences over space and time, we quantify the impacts of iodine deficiency in utero and infancy on childhood mortality and later academic achievement in Ethiopia, comparing cohorts born just before and after the May 1998 border closure that interrupted access to iodized salt. Rural children with fewer months of early-life exposure to iodized salt scored lower on standardized secondary-school exams, especially in districts with low environmental iodine, with excess deaths emerging in infancy and persisting through early childhood. These findings reveal the long-term benefits of salt iodization for health and education, especially for people with low intake of iodine from environmental sources.

Background: Intrinsic capacity (IC) is a key marker of healthy ageing, which captures an individual’s physical and mental capacities, measured across five domains: cognitive, locomotor, psychological, vitality, and sensory. Although genetic factors are known to influence both general IC and its individual domains, existing IC indices have been developed primarily using phenotypic data, without accounting for the underlying biological architecture across domains. In this study, we developed a multi-trait polygenic score (Mt-PGS) model for IC by integrating polygenic scores derived from a broad set of phenotypes spanning the five IC domains and examined its validity. Methods: Using data from 13,085 participants of the Canadian Longitudinal Study on Aging (CLSA), we computed PGSs for 63 phenotypes related to IC domains. A supervised machine-learning model was applied to develop a mt-PGS model for IC and identify the optimal set of polygenic predictors. The validity of the mt-PGS IC score was evaluated by comparing it with a phenotype-based IC score and by examining its association with mortality. Results: Our analysis identified PGSs for 33 phenotypes with non-zero coefficients, jointly explaining 2.23% of the variance in IC. Several of the strongest contributors were most closely aligned with vitality-related phenotypes in the literature (including body mass index, grip strength, fat-free mass, diastolic blood pressure, and chronic obstructive pulmonary disease), acknowledging cross-domain relevance, and that predictors from all five IC domains were represented. The mt-PGS IC score was consistent with the phenotype-based IC score, positively correlated with the phenotype-based IC score and was inversely associated with mortality (OR = 0.04; 95% CI: 0.005 – 0.379). Conclusion: Our findings support the multisystem biological basis of IC, demonstrating that an mt-PGS model integrating diverse phenotypes is associated with the phenotype-based IC score. PGSs for the phenotypes frequently related to vitality in the literature were the strongest predictors, recognizing that several of these phenotypes may span multiple domains, and that all domains contributed to the model. If replicated across different ancestries and settings, these findings may serve as a foundation for future research for the potential integration of genetic information into IC frameworks.

Intrinsic capacity (IC), which reflects the combined physical and mental reserve of an individual, is a key indicator of healthy aging. While genetic and environmental factors influence IC, the interaction effects between them remain poorly understood. This study investigated the independent and interaction effects of polygenic scores for IC (PGS-IC), socioeconomic status, and lifestyle factors on IC. Baseline data from the Canadian Longitudinal Study on Aging (CLSA; N = 13 112) were analyzed. Associations with IC (outcome) and interaction effects of PGS-IC and socioeconomic factors or lifestyle measures — including composite physical activity and diet scores — were examined using linear regression models. All models were adjusted for age and sex and, additionally, for 5 genetic principal components in models involving PGS-IC. Higher IC was associated with higher education, income, physical activity, and healthier diet patterns. Lower IC was observed among previous and current smokers and those with short (9 h) sleep durations. PGS-IC was positively associated with the IC score. Significant gene–environment interactions were identified between PGS-IC and Mediterranean diet (β = −.003, 95% CI, −0.006, −0.0002), education in younger adults (β = −.109, 95% CI, −0.211, −0.007), and sleep duration (younger adults: long sleep, β = .198, 95% CI, 0.023-0.373; older adults: short sleep, β = −.095, 95% CI, −0.153, −0.036). This study provides preliminary evidence of gene–environment interactions influencing IC, with implications for future research to determine how genetic and modifiable factors can inform strategies for maintaining IC and promoting healthy aging.

Polygenic indexes (PGIs) — DNA-based predictors of individual phenotypes — have become essential tools across biomedical and social sciences. We introduce Version 2 of the Polygenic Index Repository, which expands phenotype coverage from 47 to 61, increases the number of participating datasets from 11 to 20, and adopts a more consistent and improved methodology for PGI construction. For 16 phenotypes, we leverage summary statistics from an updated GWAS meta-analysis with greater statistical power compared to the original release, thereby improving the PGI’s predictive power. To improve power for family-based analyses, we provide imputed parental PGIs in all datasets with first-degree relatives and offer a framework for interpreting results from analyses that control for parental PGIs. We illustrate the utility of parental PGIs using two applications: (1) comparing PGI associations with and without parental PGI controls for all phenotypes in two Repository datasets with family data, and (2) for BMI and diastolic blood pressure, exploring the contribution of causal versus non-causal components of PGI associations to the imperfect portability of PGIs across subgroups within a genetic ancestry. Collectively, the updates enhance predictive performance, broaden the Repository’s scope, and introduce novel resources that reduce confounding bias and improve interpretability.

Background: Intrinsic capacity (IC) is a composite measure, computed from five domains: cognition, psychological well-being, locomotion, vitality, and sensory. IC reflects the overall physiological reserve and functional capacity of an individual, making it a key indicator of healthy ageing. The substantial interindividual variability in IC is likely influenced by genetic (polygenic) as well as socioeconomic status and lifestyle factors. However, the interaction effect of these factors is yet to be explored. Objective: This study examined (1) associations of IC with socio-economic and lifestyle factors and the polygenic scores for IC (PGS-IC) when stratified by age, and (3) the interaction effects of the PGS-IC and socio-economic or lifestyle factors on IC. Methods: Our study included 13,112 participants from the Canadian Longitudinal Study on Aging (CLSA) comprehensive cohort with complete IC variables and genetic data. Composite lifestyle scores, including the Physical Activity Scale for the Elderly (PASE), Prospective Urban Rural Epidemiological study (PURE) diet, and Mediterranean diet scores, were generated following established guidelines. Associations of IC with the socioeconomic and lifestyle factors were assessed using linear regression models adjusted for age and sex. The IC scores and the PGS-IC were developed in CLSA in our previous work, and this study tested age-stratified associations of PGS-IC with IC, and interaction effects of the PGS-IC and socioeconomic or lifestyle factors on IC using linear regression models adjusted for age, sex, and the top five genetic principal components. Statistical significance was defined as a false discovery rate (FDR) adjusted P < 0.05. Results: The mean age was 61 (standard deviation 9.6) years, and 50.8% were females. Higher IC was associated with higher education (B = 0.255, 95% CI: 0.180, 0.329), higher income (B = 0.392, CI: 0.322, 0.461), physical activity (PASE score: B = 0.001, CI: 0.0004, 0.001), and healthier diets (PURE diet score: B = 0.024, CI: 0.021, 0.027; Mediterranean diet score: B = 0.018, CI: 0.016, 0.021). IC was lower in previous (B = -0.093, CI: -0.121, -0.064) and current smokers (B = -0.407, CI: -0.459, -0.355) compared to never smokers. Likewise, short (9h: B = -0.258, CI: -0.392, -0.124) sleep durations were negatively associated with IC compared to those who had optimal sleep. The PGS-IC was positively associated with IC, particularly in younger adults. Significant interaction effects were observed with Mediterranean diet (B = -0.003, CI:-0.006 -, -0.0002) in whole sample, education in younger adults (B = -0.109, CI: -0.211 -, -0.007), and sleep (younger adults: long sleep, B = 0.198, CI:0.023, 0.373; older adults: short sleep, B = -0.095, CI: -0.153 -, -0.036). Conclusion: Novel findings confirming the interaction effects of PGS-IC with socioeconomic and lifestyle factors suggest that there is a complex interplay between genetics and the environment in shaping IC and healthy ageing.

Polygenic indexes (PGIs) trained on samples of European genetic ancestries often lose substantial predictive power when applied to non-European ancestries. While this portability problem is well recognized, its manifestation in behavioral and social traits remains understudied, and the factors driving this accuracy loss warrant more comprehensive analysis. Using data from the UK Biobank and Health and Retirement Study, we conduct a systematic analysis of PGI portability for 52 health-related, behavioral, and social phenotypes. We advance prior literature by using genome-wide PGIs, assessing cross-ancestry heritability differences, and comparing the performance of PGIs based on standard versus family-based GWAS. Our findings confirm systematic reductions in PGI predictive power for non-European ancestries—lowest in African (24%), followed by East Asian (37%) and South Asian (51%) genetic ancestries—with biologically proximal traits exhibiting greater portability than behavioral and social traits. We show that the relative importance of factors underlying reduced portability varies across traits and ancestries: in African ancestries, linkage disequilibrium and allele frequency differences explain most of the loss (82%), compared with smaller contributions in East (34%) and South Asian (25%) ancestries. Finally, we find that family-based GWAS PGIs can modestly improve portability for select traits, such as BMI in African ancestry, suggesting that part of the portability gap may reflect population-specific confounds in standard PGIs.

This study examines whether the effects of cigarette taxes on smoking behavior vary by an individual’s genetic predisposition and the timing of policy exposure. Using data from the U.S. Health and Retirement Study, we link historical state-level cigarette excise taxes with polygenic indices (PGIs) for smoking behavior. We find that the timing of tax exposure has distinct effects on different margins of smoking behavior: taxes experienced during adolescence primarily influence long-term smoking participation, while taxes in older adulthood more strongly affect smoking intensity. Our key finding is a significant interaction between adolescent-era taxes and genetic risk. The smoking reduction caused by adolescent taxes is significantly greater for individuals with a higher genetic predisposition to smoke. Conversely, we find no evidence that the effects of taxes in older age are moderated by genetic risk. These results indicate that youth-targeted tax policies are particularly effective for genetically at-risk individuals, and that studies overlooking this heterogeneity may underestimate the long-run benefits of these interventions.

Polygenic indexes (PGIs) trained on samples of European genetic ancestries often lose substantial predictive power when applied to non-European ancestries. While this portability problem is well recognized, its manifestation in behavioral and social traits remains understudied, and the factors driving this accuracy loss warrant more comprehensive analysis. Using data from the UK Biobank and Health and Retirement Study, we conduct a systematic analysis of PGI portability for 52 health-related, behavioral, and social phenotypes. We advance prior literature by using genome-wide PGIs, assessing cross-ancestry heritability differences, and comparing the performance of PGIs based on standard versus family-based GWAS. Our findings confirm systematic reductions in PGI predictive power for non-European ancestries—with relative accuracy being lowest in African (24%), followed by East Asian (37%) and South Asian (51%) genetic ancestries. We also find that biologically proximal traits exhibit greater portability than behavioral and social traits. We show that the relative importance of factors underlying reduced portability varies across traits and ancestries: in African ancestries, linkage disequilibrium and allele frequency differences explain most of the loss (82%), compared with smaller contributions in East (34%) and South Asian (25%) ancestries. Finally, we find that family-based GWAS PGIs can modestly improve portability for select traits, such as BMI in African ancestry, suggesting that part of the portability gap may reflect population-specific confounds in standard PGIs.

Background: This study explores the magnitude and timing of sex and gender disparities in child development by describing differences in health outcomes for male and female siblings, comparing twins to control for all aspects of life circumstances other than sex and gender.Methods: We construct a repeat cross‐sectional dataset of 191 838 twins among 1.7 million births recorded in 214 nationally representative household surveys for 72 countries between 1990 and 2016. To test for biological or social mechanisms that might favor the health of male or female infants, we describe differences in birthweights, attained heights, weights, and survival to distinguish gestational health from care practices after each child is born.Results: We find that male fetuses grow at the expense of their co‐twin, significantly reducing their sibling's birthweight and survival probabilities, but only if the other fetus is male. Female fetuses are born significantly heavier when they share the uterus with a male co‐twin and have no significant difference in survival probability whether they happen to draw a male or a female co‐twin. These findings demonstrate that sex‐specific sibling rivalry and male frailty begin in utero, prior to gender bias after birth that typically favors male children.Conclusions: Sex differences in child health may have competing effects with gender bias that occurs during childhood. Worse health outcomes for males with a male co‐twin could be linked to hormone levels or male frailty, and could lead to underestimates of the effect sizes of later gender bias against girls. Gender bias favoring surviving male children may explain the lack of differences in height and weight observed for twins with either male or female co‐twins.