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Background: We aimed to evaluate the impacts of metabolomic body mass index (metBMI) phenotypes on the risks of cardiovascular and ocular diseases outcomes. Methods: This study included cohorts in UK and Guangzhou, China. By leveraging the serum metabolome and BMI data from UK Biobank, this study developed and validated a metBMI prediction model using a ridge regression model among 89,830 participants based on 249 metabolites. Five obesity phenotypes were obtained by metBMI and actual BMI (actBMI): normal weight (NW, metBMI of 18.5–24.9 kg/m2), overweight (OW, metBMI of 25–29.9 kg/m2), obesity (OB, metBMI ≥ 30 kg/m2), overestimated (OE, metBMI-actBMI > 5 kg/m2), and underestimated (UE, metBMI-actBMI < − 5 kg/m2). Additional participants from the Guangzhou Diabetes Eye Study (GDES) were included for validating the hypothesis. Outcomes included all-cause and cardiovascular (CVD)-cause mortality, as well as incident CVD (coronary heart disease, heart failure, myocardial infarction [MI], and stroke) and age-related eye diseases (age-related macular degeneration [AMD], cataracts, glaucoma, and diabetic retinopathy [DR]). Results: In the UKB, although OE group had lower actBMI than NW group, the OE group had a significantly higher risk of all-cause mortality than those in NW prediction group (HR, 1.68; 95% CI 1.16–2.43). Similarly, the OE group had a 1.7–3.6-fold higher risk than their NW counterparts for cardiovascular mortality, heart failure, myocardial infarction, and coronary heart disease (all P < 0.05). In addition, risk of age-related macular denegation (HR, 1.96; 95% CI 1.02–3.77) was significantly higher in OE group. In the contrast, UE and OB groups showed similar risks of mortality and of cardiovascular and age-related eye diseases (all P > 0.05), though the UE group had significantly higher actBMI than OB group. In the GDES cohort, we further confirmed the potential of metabolic BMI (metBMI) fingerprints for risk stratification of cardiovascular diseases using a different metabolomic approach. Conclusions: Gaps of metBMI and actBMI identified novel metabolic subtypes, which exhibit distinctive cardiovascular and ocular risk profiles. The groups carrying obesity-related metabolites were at higher risk of mortality and morbidity than those with normal health metabolites. Metabolomics allowed for leveraging the future of diagnosis and management of 'healthily obese' and 'unhealthily lean' individuals. [ABSTRACT FROM AUTHOR]

The prevalence of myopia, or nearsightedness, has skyrocketed in the past few decades, creating a public health crisis that is commonly attributed to lifestyle changes. Here we report an overall increase in the frequencies of myopia-associated mutant alleles over 25 years among participants of the UK Biobank. Although myopia itself appears to be selected against, many of the mutant alleles are associated with reproductive benefits, suggesting that reproduction-related selection inadvertently contributes to the myopia epidemic. We estimate that, in the UK alone, natural selection adds more than 100 000 myopia cases per generation, and argue that antagonistic pleiotropy be broadly considered in explaining the spreads of apparently disadvantageous phenotypes in humans and beyond. [ABSTRACT FROM AUTHOR]

There is evidence in humans for genetic influences on the probability (P boy) that a birth yields a boy instead of a girl [ 1–6 ], suggesting a potential variation of P boy among families. To quantify this variation, we analyze the survey data from over 300,000 UK Biobank participants primarily born between 1940 and 1970 [ 7 ]. Surprisingly, the proportion of male children in a family, or sex ratio (SR), has a significantly smaller among-family variation than expected under a uniform P boy. We propose that this phenomenon results from reproductive behaviors reflecting a preference for having children of both sexes, much like the coupon collector's problem in probability theory where collecting a complete set of distinct coupons is considered a win. We find that the observed deficit in SR variation is explainable by 3.3% of "coupon-collecting" families. Consistently, significantly more families than expected have all children of the same sex except for the child born last. This trend is more pronounced in the late than the early half of the families in the data, suggesting an increasing popularity of this behavior. Analysis of a Dutch genealogical dataset spanning the past 4 centuries reveals higher-than-expected SR variations over much of the history; only after 1940 did the SR variation drop below the expectation. We conclude that a significant fraction of couples now exhibit the coupon collection behavior in reproduction such that SR is more homogeneous among families than expected by chance. • Sex ratio variation among families in the UK is smaller than the random expectation • This phenomenon is explained by the coupon collection behavior in reproduction • The popularity of the behavior rose during the 3 decades examined (1940s–1960s) • Over the past 400 years in the Netherlands, this phenomenon is seen only after 1940 Long and Zhang report that the proportion of male children in a family is more homogenous among families than expected by chance, a phenomenon caused by the "coupon-collection" reproductive behavior of not stopping reproducing until having had children of both sexes. This behavior has become apparent only since the mid-20th century. [ABSTRACT FROM AUTHOR]