Identification of type 2 diabetes loci in 433,540 East Asian individuals.

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues4-6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.

Ultraprocessed Food Intake during the Transition to Adulthood Varies According to Sociodemographic Characteristics and Maternal Intake in Cebu, Philippines.

BACKGROUND: Ultraprocessed foods (UPFs) are associated with elevated risk of noncommunicable disease, but little is known about UPF intake and the individual-, household-, and community-level factors associated with it among adolescents in low- or middle-income countries. OBJECTIVES: We estimated the association of UPF intake across adolescence with sociodemographic characteristics and maternal UPF intake in a Filipino cohort. METHODS: Data were from 4 waves (1994-2005) of the Cebu Longitudinal Health and Nutrition Survey (n = 2068); participants were aged 11, 15, 18, and 21 y. Foods from 24-h recalls were classified using NOVA. We used two-part multilevel models to estimate time-varying associations of the odds and amount (percentage daily kilocalories) of UPF intake with sociodemographic characteristics and maternal UPF intake (none, below median among UPF-consuming mothers ["low"], at or above median ["high"]). RESULTS: Median UPF intake (interquartile range [IQR]) among adolescents was 7.3% (IQR: 0, 17.2%) of daily kilocalories at age 11 y and 10.6% (IQR: 3.6, 19.6%) at 21 y. The odds and amount of adolescent UPF intake were positively associated with female sex, years of schooling, and household wealth and inversely associated with household size. The odds-but not amount-of adolescent UPF intake was positively associated with maternal education and urbanicity and inversely associated with the distance from a household's primary store/market. The association between odds of adolescent UPF intake and school enrollment was positive in adolescence but disappeared in early adulthood. Compared with offspring whose mothers did not consume UPFs, the odds of UPF intake among those whose mothers had low or high UPF intake was greater in adolescence, but there was no association once offspring became adults. At all ages, maternal UPF intake was positively associated with the amount of offspring intake. CONCLUSIONS: Adolescent UPF intake varied across sociodemographic characteristics and was positively associated with maternal UPF intake, but not after adolescents entered adulthood.

Socioeconomic status is negatively associated with immunosenescence but positively associated with inflammation among middle-aged women in Cebu, Philippines.

BACKGROUND: Socioeconomic status (SES) gradients in health are well-documented, and while biological pathways are incompletely understood, chronic inflammation and accelerated immune aging (immunosenescence) among lower SES individuals have been implicated. However, previous findings have come from samples in higher income countries, and it is unclear how generalizable they are to lower- and middle-income countries (LMIC) with different infectious exposures and where adiposity-an important contributor to chronic inflammation-might show different SES patterning. To address this gap, we explored associations between SES and inflammation and immunosenescence in a sample of women in Cebu, Philippines. METHODS: Data came from the mothers of the Cebu Longitudinal Health and Nutrition Survey birth cohort (mean age: 47.7, range: 35-69 years). SES was measured as a combination of annual household income, education level, and assets. Chronic inflammation was measured using C-reactive protein (CRP) in plasma samples from 1,834 women. Immunosenescence was measured by the abundance of exhausted CD8T (CD8 + CD28-CD45RA-) and naïve CD8T and CD4T cells, estimated from DNA methylation in whole blood in a random subsample of 1,028. Possible mediators included waist circumference and a collection of proxy measures of pathogen exposure. RESULTS: SES was negatively associated with the measures of immunosenescence, with slight evidence for mediation by a proxy measure for pathogen exposure from the household's drinking water source. In contrast, SES was positively associated with CRP, which was explained by the positive association with waist circumference. CONCLUSIONS: Similar to higher income populations, in Cebu there is an SES-gradient in pathogen exposures and immunosenescence. However, lifestyle changes occurring more rapidly among higher SES individuals is contributing to a positive association between SES and adiposity and inflammation. Our results suggest more studies are needed to clarify the relationship between SES and inflammation and immunosenescence across LMIC.

Dietary quality and dietary greenhouse gas emissions in the USA: a comparison of the planetary health diet index, healthy eating index-2015, and dietary approaches to stop hypertension.

BACKGROUND: The Planetary Health Diet Index (PHDI) measures adherence to the dietary pattern presented by the EAT-Lancet Commission, which aligns health and sustainability targets. There is a need to understand how PHDI scores correlate with dietary greenhouse gas emissions (GHGE) and how this differs from the carbon footprints of scores on established dietary recommendations. The objectives of this study were to compare how the PHDI, Healthy Eating Index-2015 (HEI-2015) and Dietary Approaches to Stop Hypertension (DASH) relate to (a) dietary GHGE and (b) to examine the influence of PHDI food components on dietary GHGE. METHODS: We used life cycle assessment data from the Database of Food Recall Impacts on the Environment for Nutrition and Dietary Studies to calculate the mean dietary GHGE of 8,128 adult participants in the 2015-2016 and 2017-2018 cycles of the National Health and Nutrition Examination Survey (NHANES). Poisson regression was used to estimate the association of (a) quintiles of diet score and (b) standardized dietary index Z-scores with dietary GHGE for PHDI, HEI-2015, and DASH scores. In secondary analyses, we used Poisson regression to assess the influence of individual PHDI component scores on dietary GHGE. RESULTS: We found that higher dietary quality on all three indices was correlated with lower dietary GHGE. The magnitude of the dietary quality-dietary GHGE relationship was larger for PHDI [-0.4, 95% CI (-0.5, -0.3) kg CO2 equivalents per one standard deviation change] and for DASH [-0.5, (-0.4, -0.6) kg CO2-equivalents] than for HEI-2015 [-0.2, (-0.2, -0.3) kg CO2-equivalents]. When examining PHDI component scores, we found that diet-related GHGE were driven largely by red and processed meat intake. CONCLUSIONS: Improved dietary quality has the potential to lower the emissions impacts of US diets. Future efforts to promote healthy, sustainable diets could apply the recommendations of the established DASH guidelines as well as the new guidance provided by the PHDI to increase their environmental benefits.

Intimate partner violence, depression, and chronic low-grade inflammation among middle-aged women in Cebu, Philippines.

OBJECTIVES: Recent discussions in human biology have highlighted how local ecological contexts shape the relationship between social stressors and health across populations. Chronic low-grade inflammation has been proposed as a pathway linking social stressors to health, with evidence concentrated in high-income Western contexts. However, it remains unclear whether this is an important pathway in populations where prevalence is lower due to lower adiposity and greater infectious exposures. To investigate this further, we tested associations between multiple types of intimate partner violence (IPV), a highly prevalent stressor and health crisis globally, and C-reactive protein (CRP), a commonly used measure of chronic low-grade inflammation, in Cebu, Philippines. For reference, we compared results for CRP to depression, a well-established and consistently observed health outcome of IPV. METHODS: Data came from 1601 currently partnered women (ages 35-69 years) as part of the Cebu Longitudinal Health and Nutrition Survey. IPV exposures included physical, emotional, and controlling behavior. Depression scores were measured using a modified version of the Center for Epidemiologic Studies-Depression Scale for this population, whereas plasma CRP was measured from overnight-fasted morning blood samples. RESULTS: All three types of IPV were associated with a higher depression score. However, none of the IPV measures were associated with CRP. In a post hoc interaction test, emotional IPV became positively associated with CRP as waist circumference increased above the mean. CONCLUSIONS: Our results suggest a complex relationship between social stressors and chronic low-grade inflammation, which is likely dependent on the population-specific context of lifestyle and environmental factors.

Awareness, experiences, and beliefs related to ultra-processed foods among young people in Cebu, Philippines.

Ultra-processed food (UPF) intake is rising in low- and middle-income countries, where non-communicable diseases are now the leading contributor to disease burden. The purpose of this study was to assess awareness and knowledge of UPFs, factors that influence consumption of UPFs, and beliefs about the relationship between UPF intake and health among young people (18-20 years old) in a metropolitan area of the Philippines, a lower middle-income country. We conducted eight focus group discussions across four strata defined by gender and urban-rural neighborhood designation. We applied deductive and inductive codes to transcripts and organized codes into themes. Sixty participants were included in the study. Although most were unfamiliar with the concept of UPFs, participants demonstrated an intuitive understanding of the meaning of the term. Vendors in or around schools were commonly reported as a source of UPFs, though most participants reported consuming UPFs at home as well. Factors that were reported as having influence over participants' UPF intake included taste, convenience, cost, influence from parents, peers, and others, and health knowledge and status. Participants expressed various beliefs about the link between overconsumption of UPFs and risk of multiple health outcomes, including diabetes, hypertension, and kidney disease. Some males, but not females, believed that some UPFs were neutral or beneficial with respect to health. Commonly cited sources of information about UPFs and their link to health included parents, schools, and social media. This study provides important insights into the factors that drive UPF consumption among young people in a lower middle-income country and should inform efforts to reduce UPF intake among young people in this and similar settings.

Effects of early-life poverty on health and human capital in children and adolescents: analyses of national surveys and birth cohort studies in LMICs.

The survival and nutrition of children and, to a lesser extent, adolescents have improved substantially in the past two decades. Improvements have been linked to the delivery of effective biomedical, behavioural, and environmental interventions; however, large disparities exist between and within countries. Using data from 95 national surveys in low-income and middle-income countries (LMICs), we analyse how strongly the health, nutrition, and cognitive development of children and adolescents are related to early-life poverty. Additionally, using data from six large, long-running birth cohorts in LMICs, we show how early-life poverty can have a lasting effect on health and human capital throughout the life course. We emphasise the importance of implementing multisectoral anti-poverty policies and programmes to complement specific health and nutrition interventions delivered at an individual level, particularly at a time when COVID-19 continues to disrupt economic, health, and educational gains achieved in the recent past.

Health and development from preconception to 20 years of age and human capital.

Optimal health and development from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualises the major influences during periods of development from preconception, through pregnancy, childhood, and adolescence that affect human capital. In addition to mortality in children younger than 5 years, stillbirths and deaths in 5-19-year-olds are important to consider. The global rate of mortality in individuals younger than 20 years has declined substantially since 2000, yet in 2019 an estimated 8·6 million deaths occurred between 28 weeks of gestation and 20 years of age, with more than half of deaths, including stillbirths, occurring before 28 days of age. The 1000 days from conception to 2 years of age are especially influential for human capital. The prevalence of low birthweight is high in sub-Saharan Africa and even higher in south Asia. Growth faltering, especially from birth to 2 years, occurs in most world regions, whereas overweight increases in many regions from the preprimary school period through adolescence. Analyses of cohort data show that growth trajectories in early years of life are strong determinants of nutritional outcomes in adulthood. The accrual of knowledge and skills is affected by health, nutrition, and home resources in early childhood and by educational opportunities in older children and adolescents. Linear growth in the first 2 years of life better predicts intelligence quotients in adults than increases in height in older children and adolescents. Learning-adjusted years of schooling range from about 4 years in sub-Saharan Africa to about 11 years in high-income countries. Human capital depends on children and adolescents surviving, thriving, and learning until adulthood.

Growth in Infancy and Childhood and Age at Menarche in Five Low- or Middle-Income Countries: Consortium of Health Orientated Research in Transitional Societies (COHORTS).

BACKGROUND: Earlier age at menarche is associated with behavioral and noncommunicable disease risks. The influence of birth weight (BW) (intrauterine) and postnatal growth on age at menarche is not well studied in low- and middle-income countries (LMICs). OBJECTIVE: Therefore, we investigated these associations in 5 LMIC birth cohorts. METHODS: We analyzed data from Brazil, Guatemala, India, the Philippines, and South Africa (n = 3983). We derived stunting (< -2 SD scores) at 24 mo using the WHO child growth standards. We generated interaction terms with categorized BW and conditional weight (lighter < 0 or heavier ≥ 0), and height (shorter < 0 or taller ≥ 0) z-scores. We categorized early-, modal-, and late-onset menarche and used multilevel ordinal regression. We used multilevel linear regression on continuous age at menarche. RESULTS: Mean age at menarche was 12.8 y (95% CI: 12.7 12.9). BW was not associated with age at menarche. Conditional height at 24 mo and mid-childhood (OR: 1.35; 95% CI: 1.27, 1.44 and 1.32; 1.25, 1.41, respectively) and conditional weight at 24 mo and mid-childhood (OR: 1.15; 1.08, 1.22 and 1.18; 1.11, 1.25, respectively) were associated with increased likelihood of early-onset menarche. Being heavier at birth and taller at 24 mo was associated with a 4-mo (95% CI: 0.8, 7.6) earlier age at menarche than being lighter at birth and shorter at 24 mo. Being heavier at birth but lighter in mid-childhood was associated with a 3-mo (95% CI: 0.8, 4.8) later age at menarche than being lighter at birth and mid-childhood. Age at menarche was 7 mo later in stunted than nonstunted girls. CONCLUSION: Age at menarche is inversely related to relative weight gain but also to rapid linear growth among those born shorter but remained stunted, and those born taller and grew excessively. These findings do not deter the global health goal to reduce growth faltering but emphasize the potential adverse effects of an obesogenic environment on adolescent development.

Quality of vital event data for infant mortality estimation in prospective, population-based studies: an analysis of secondary data from Asia, Africa, and Latin America.

INTRODUCTION: Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases. METHODS: We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data. RESULTS: Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources. CONCLUSIONS: Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly.

Rare and low-frequency coding variants alter human adult height.

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

Early life predictors of body composition trajectories from adolescence to mid-adulthood.

OBJECTIVES: Guatemala has experienced rapid increases in adult obesity. We characterized body composition trajectories from adolescence to mid-adulthood and determined the predictive role of parental characteristics, early life factors, and a nutrition intervention. METHODS: One thousand three hundred and sixty-four individuals who participated as children in a nutrition trial (1969-1977) were followed prospectively. Body composition characterized as body mass index (BMI), fat mass index (FMI), and fat-free mass indices (FFMI), was available at four ages between 10 and 55 years. We applied latent class growth analysis to derive sex-specific body composition trajectories. We estimated associations between parental (age, height, schooling) and self-characteristics (birth order, socioeconomic status, schooling, and exposure to a nutrition supplement) with body composition trajectories. RESULTS: In women, we identified two latent classes of FMI (low: 79.6%; high: 20.4%) and BMI (low: 73.0%; high: 27.0%), and three of FFMI (low: 20.2%; middle: 55.9%; high: 23.9%). In men, we identified two latent classes of FMI (low: 79.6%; high: 20.4%) and FFMI (low: 62.4%; high: 37.6%), and three of BMI (low: 43.1%; middle: 46.9%; high: 10.0%). Among women, self's schooling attainment inversely predicted FMI (OR [being in a high latent class]: 0.91, 95% CI: 0.85, 0.97), and maternal schooling positively predicted FFMI (OR: 1.16, 95% CI: 0.97, 1.39). Among men, maternal schooling, paternal age, and self's schooling attainment positively predicted FMI. Maternal schooling positively predicted FFMI, whereas maternal age and paternal schooling were inverse predictors. The nutrition intervention did not predict body composition class membership. CONCLUSIONS: Parents' age and schooling, and self's schooling attainment are small but significant predictors of adult body composition trajectories.

Association between infectious exposures in infancy and epigenetic age acceleration in young adulthood in metropolitan Cebu, Philippines.

OBJECTIVES: The drivers of human life expectancy gains over the past 200 years are not well-established, with a potential role for historical reductions in infectious disease. We investigate whether infectious exposures in infancy predict biological aging using DNA methylation-based markers that forecast patterns of morbidity and mortality later in life. METHODS: N = 1450 participants from the Cebu Longitudinal Health and Nutrition Survey-a prospective birth cohort initiated in 1983-provided complete data for the analyses. Mean chronological age was 20.9 years when venous whole blood samples were drawn for DNA extraction and methylation analysis, with subsequent calculation of three epigenetic age markers: Horvath, GrimAge, and DunedinPACE. Unadjusted and adjusted least squares regression models were evaluated to test the hypothesis that infectious exposures in infancy are associated with epigenetic age. RESULTS: Birth in the dry season, a proxy measure for increased infectious exposure in the first year of life, as well as the number of symptomatic infections in the first year of infancy, predicted lower epigenetic age. Infectious exposures were associated with the distribution of white blood cells in adulthood, which were also associated with measures of epigenetic age. CONCLUSIONS: We document negative associations between measures of infectious exposure in infancy and DNA methylation-based measures of aging. Additional research, across a wider range of epidemiological settings, is needed to clarify the role of infectious disease in shaping immunophenotypes and trajectories of biological aging and human life expectancy.

Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology.

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

Dietary Patterns and Years Living in the United States by Hispanic/Latino Heritage in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: Previous diet findings in Hispanics/Latinos rarely reflect differences in commonly consumed and culturally relevant foods across heritage groups and by years lived in the United States. OBJECTIVES: We aimed to identify and compare a posteriori heritage-specific dietary patterns (DPs) and evaluate their associations with "healthfulness" [using the Alternative Healthy Eating Index-2010 (AHEI-2010)] and years living in the United States. METHODS: We used baseline data from a population-based cohort of 14,099 Hispanics/Latinos aged 18-74 y in the Hispanic Community Health Study/Study of Latinos. We performed principal factor analysis using two 24-h recalls to derive DPs, separately, in each heritage group (Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American), and identified overarching DPs based on high-loading foods shared by ≥2 groups. We used multivariable linear regression to test associations of DPs with AHEI-2010 and years living in the United States. RESULTS: We identified 5 overarching DPs (Burgers, Fries, & Soft Drinks; White Rice, Beans, & Red Meats; Fish; Egg & Cheese; and Alcohol). All Burgers, Fries, & Soft Drinks DPs were inversely associated with AHEI-2010, whereas all Fish DPs (except Dominican) were positively associated with this index (all P-trend < 0.001). White Rice, Beans, & Red Meats DPs showed inverse associations in Cuban and Central American groups and positive associations in Mexican-origin individuals (all P-trend < 0.001). Fewer years living in the United States was associated with higher scores for White Rice, Beans, & Red Meats DPs in Cuban and Mexican heritage groups and lower scores on Burgers, Fries, & Soft Drinks DPs in Cuban, Mexican, and Puerto Rican groups (all P-trend < 0.01). CONCLUSIONS: Our findings show substantial variation in DPs across Hispanics/Latinos and adherence to DPs by time in the United States, which could inform dietary interventions targeting this diverse US population. This trial was registered at clinicaltrials.gov as NCT02060344.

Patterns of Growth in Childhood in Relation to Adult Schooling Attainment and Intelligence Quotient in 6 Birth Cohorts in Low- and Middle-Income Countries: Evidence from the Consortium of Health-Oriented Research in Transitioning Societies (COHORTS).

BACKGROUND: Growth faltering has been associated with poor intellectual performance. The relative strengths of associations between growth in early and in later childhood remain underexplored. OBJECTIVES: We examined the association between growth in childhood and adult human capital in 5 low- and middle-income countries (LMICs). METHODS: We analyzed data from 9503 participants in 6 prospective birth cohorts from 5 LMICs (Brazil, Guatemala, India, the Philippines, and South Africa). We used linear and quasi-Poisson regression models to assess the associations between measures of height and relative weight at 4 age intervals [birth, age ∼2 y, midchildhood (MC), adulthood] and 2 dimensions of adult human capital [schooling attainment and Intelligence Quotient (IQ)]. RESULTS: Meta-analysis of site- and sex-specific estimates showed statistically significant associations between size at birth and height at ∼2 y and the 2 outcomes (P < 0.001). Weight and length at birth and linear growth from birth to ∼2 y of age (1 z-score difference) were positively associated with schooling attainment (ß: 0.13; 95% CI: 0.08, 0.19, ß: 0.17; 95% CI: 0.07, 0.32, and ß: 0.25, 95% CI: 0.10, 0.40, respectively) and adult IQ (ß: 0.74, 95% CI: 0.35, 1.14, ß: 0.73, 95% CI: 0.35, 1.10, and ß: 1.52, 95% CI: 0.96, 2.08, respectively). Linear growth from age 2 y to MC and from MC to adulthood was not associated with higher school attainment or IQ. Change in relative weight in early childhood, MC, and adulthood was not associated with either outcome. CONCLUSIONS: Linear growth in the first 1000 d is a predictor of schooling attainment and IQ in adulthood in LMICs. Linear growth in later periods was not associated with either of these outcomes. Changes in relative weight across the life course were not associated with schooling and IQ in adulthood.

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets.

Decreased consumption of common weaning foods is associated with poor linear growth among HIV-exposed infants participating in the Kigali antiretroviral and breastfeeding assessment for the elimination of HIV (Kabeho) study.

OBJECTIVE: The World Health Organization recommends that complementary foods that are adequate, safe, and appropriate be introduced to infants at age 6 months. Using an innovative modeling technique, we examine patterns of nutrient intake in HIV-exposed and uninfected (HEU) infants and establish their relationship with growth. METHODS: Single-day dietary recalls and anthropometrics were collected every two to 3 months from 543 infants living in Kigali, Rwanda, and attending clinics for the prevention of mother-to-child HIV transmission. A common weaning food index (CWFI) was calculated in grams and nutrient density for infants to reflect the extent to which the infants consumed the weaning foods typical of this population at ages 6 to 10, 11 to 15, and 16 to 20 months. Regressions among the CWFI, length-for-age z-scores (LAZ), and weight-for-length z-scores (WLZ) were conducted to estimate the relationship between the dietary patterns and growth. RESULTS: Mean absolute intake of zinc and calcium from complementary foods was insufficient. Increasing CWFI was related to increasing cow milk consumption. The density CWFI showed a decrease in the density of iron and folate as infants consume more of the weaning foods typical of this population. Density CWFI, breastfeeding, and caloric intake act on early LAZ and WLZ and interact with one another. Among breastfed infants, those who consume little of the common weaning foods and have a high caloric intake develop deficits in LAZ and have an elevated WLZ. CONCLUSIONS: A diet that is more dominated by the typical weaning foods of this population may support a healthy growth pattern.

Ankle brachial index (ABI) in a cohort of older women in the Philippines: Prevalence of peripheral artery disease and predictors of ABI.

OBJECTIVE: Cardiovascular disease (CVD) is rising in low and middle-income countries, but studies of CVD epidemiology in such settings often focus on risk factors rather than measures of disease progression. Here we use the ankle brachial index (ABI) to assess the prevalence of peripheral artery disease (PAD) among older women living in Metropolitan Cebu, Philippines, and relationships between ABI and CVD risk factors and body composition. METHODS: ABI was measured using the Doppler technique in 538 female participants in the 2015 Cebu Longitudinal Health and Nutrition Survey (mean age 58 years, range 47-78 years). ABI was related to a panel of CVD risk factors measured in 2005 and 2012, and to 2012 body composition measures. RESULTS: The prevalence of PAD (1.8%) was among the lowest reported in any comparably-aged sample, and only 9.9% of participants had an ABI indicating borderline PAD risk. Smoking (P < 0.011) and use of CVD medications (P < 0.0001) predicted lower ABI (indicating higher PAD risk), which was also lower in relation to 2012 systolic blood pressure (P < 0.054). ABI was unrelated to other CVD risk factors. An apparent protective relationship between body mass index (BMI) and ABI, noted in previous studies, was found to be confounded by protective relationships between ABI and fat free mass, height, and grip strength (all P < 0.05). CONCLUSIONS: The prevalence of PAD is low in Cebu Longitudinal Health and Nutrition Survey participants, and ABI was related to few CVD risk factors. Past reports of lower PAD risk in relation to BMI may reflect confounding by lean mass, which has protective relationships with ABI.

Determinants of growth in HIV-exposed and HIV-uninfected infants in the Kabeho Study.

HIV-exposed and HIV-uninfected (HEU) infants may be at increased risk of poor health and growth outcomes. We characterized infant growth trajectories in a cohort of HEU infants to identify factors associated with healthy growth. HIV-positive women participating in prevention of mother-to-child HIV transmission programmes in Kigali, Rwanda, were followed until their infants were 2 years old. Infant anthropometrics were regularly collected. Latent class analysis was used to categorize infant growth trajectories. Multiple logistic regression was used to estimate the odds of infants belonging to each growth trajectory class. On average, this population of HEU infants had moderate linear growth faltering, but only modest faltering in weight, resulting in mean weight-for-length z-score (WLZ) above the World Health Organization (WHO) median. Mean WLZ was 0.53, and mean length-for-age z-score (LAZ) was -1.14 over the first 2 years of life. We identified four unique WLZ trajectories and seven trajectories in LAZ. Low neonatal weight-for-age and a high rate of illness increased the likelihood that infants were in the lightest WLZ class. Shorter mothers were more likely to have infants with linear growth faltering. Female infants who were older at the end of exclusive breastfeeding were more likely to be in the second tallest LAZ class. In conclusion, the current WHO recommendations of Option B+ and extended breastfeeding may induce higher WLZ and lower LAZ early in infancy. However, there is considerable heterogeneity in growth patterns that is obscured by simply analysing average growth trends, necessitating the analysis of growth in subpopulations.