Polycystic Ovary Syndrome, Metabolic Syndrome, and Inflammation in the Hispanic Community Health Study/Study of Latinos.

CONTEXT: Polycystic Ovary Syndrome (PCOS) is a multifaceted endocrine disorder with reproductive and metabolic dysregulation. PCOS has been associated with inflammation and Metabolic Syndrome (MetS); however, the moderating effects of inflammation as measured by C-reactive protein (CRP) and menopause on the PCOS-MetS association have not been studied in Hispanic/Latinas with PCOS who have a higher metabolic burden. OBJECTIVE: We studied the cross-sectional association between PCOS and (i) MetS in 7316 females of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), (ii) subcomponents of MetS including impaired fasting glucose (IFG) and elevated triglycerides (TGL), and (iii) effect modification by menopausal status and CRP. DESIGN: HCHS/SOL is a multicenter, longitudinal, and observational study of US Hispanic/Latinos. Our study sample included females from Visit 2 with self-reported PCOS and MetS (ages 23-82 years). RESULTS: PCOS (prevalence=18.8%) was significantly associated with MetS prevalence (OR=1.41[95% confidence interval: 1.13-1.76]), IFG and TGL (OR=1.42[1.18-1.72], OR=1.48[1.20-1.83] respectively). We observed effect modification by menopausal status (ORpre=1.46, pint=0.02; ORpost=1.34, pint=0.06) and CRP (ORelevated=1.41, pint=0.04; ORnormal=1.26, pint=0.16) on the PCOS-MetS association. We also observed a super-additive interaction between CRP and PCOS, adjusting for which resulted in an attenuated effect of PCOS on MetS (OR=1.29[0.93-1.78]). CONCLUSIONS: Hispanic/Latino females with PCOS had higher odds of MetS, IFG, and elevated TGL, than their peers without PCOS. Interaction analyses revealed that the odds of MetS are higher among PCOS females who have pre-menopausal status or high inflammation. Interventions in Hispanic/Latinas should target these outcomes for effective management of the disease.

Does biological age mediate the relationship between childhood adversity and depression? Insights from the Detroit Neighborhood Health Study.

The link between childhood adversity and adulthood depression is well-established; however, the underlying mechanisms are still being explored. Recent research suggests biological age may mediate the relationship between childhood adversity and depression in later life. This study examines if biological age mediates the relationship between childhood adversity and depression symptoms using an expanded set of biological age measures in an urban population-based cohort. Data from waves 1-3 of the Detroit Neighborhood Health Study (DNHS) were used in this analysis. Questions about abuse during childhood were coded to form a childhood adversity score similar to the Adverse Childhood Experience measure. Multiple dimensions of biological age, defined as latent variables, were considered, including systemic biological age (GrimAge, PhenoAge), epigenetic age (Horvath, SkinBlood), and immune age (cytomegalovirus, herpes simplex virus type 1, C-reactive protein, interleukin-6). Depression symptoms, modeled as a latent variable, were captured through the Patient Health Questionnaire-9 (PHQ-9). Models were adjusted for age, gender, race, parent education, and past depressive symptoms. Total and direct effects of childhood adversity on depression symptoms and indirect effects mediated by biological age were estimated. For total and direct effects, we observed a dose-dependent relationship between cumulative childhood adversity and depression symptoms, with emotional abuse being particularly influential. However, contrary to prior studies, in this sample, we found few direct effects of childhood adversity on biological age or biological age on depression symptoms and no evidence of mediation through the measures of biological age considered in this study. Further research is needed to understand how childhood maltreatment experiences are embodied to influence health and wellness.

Assessing efficiency of fine-mapping obesity-associated variants through leveraging ancestry architecture and functional annotation using PAGE and UKBB cohorts.

Inadequate representation of non-European ancestry populations in genome-wide association studies (GWAS) has limited opportunities to isolate functional variants. Fine-mapping in multi-ancestry populations should improve the efficiency of prioritizing variants for functional interrogation. To evaluate this hypothesis, we leveraged ancestry architecture to perform comparative GWAS and fine-mapping of obesity-related phenotypes in European ancestry populations from the UK Biobank (UKBB) and multi-ancestry samples from the Population Architecture for Genetic Epidemiology (PAGE) consortium with comparable sample sizes. In the investigated regions with genome-wide significant associations for obesity-related traits, fine-mapping in our ancestrally diverse sample led to 95% and 99% credible sets (CS) with fewer variants than in the European ancestry sample. Lead fine-mapped variants in PAGE regions had higher average coding scores, and higher average posterior probabilities for causality compared to UKBB. Importantly, 99% CS in PAGE loci contained strong expression quantitative trait loci (eQTLs) in adipose tissues or harbored more variants in tighter linkage disequilibrium (LD) with eQTLs. Leveraging ancestrally diverse populations with heterogeneous ancestry architectures, coupled with functional annotation, increased fine-mapping efficiency and performance, and reduced the set of candidate variants for consideration for future functional studies. Significant overlap in genetic causal variants across populations suggests generalizability of genetic mechanisms underpinning obesity-related traits across populations.

Childhood and Life-Course Socioeconomic Position and Cognitive Function in the Adult Population of the Hispanic Community Health Study/Study of Latinos.

The Hispanic/Latino population experiences socioeconomic adversities across the lifespan and is at greater risk of cognitive impairment, yet little is known about the role of life-course socioeconomic position (SEP) in cognitive function in this population. Using baseline data (2008-2011) from adults (aged 45-74 years) of the Hispanic Community Health Study/Study of Latinos, we assessed the association between childhood SEP and socioeconomic mobility with cognitive function, and whether this association was mediated by midlife SEP. Childhood SEP was assessed using parental education. An index combining participants' education and household income represented midlife SEP. Socioeconomic mobility was categorized as stable low, downward or upward mobility, and stable high-SEP. Cognitive function measures were modeled using survey linear regression with inverse-probability weighting, accounting for covariates. We used mediation analysis to estimate the indirect effect of childhood SEP on cognition through midlife SEP. High childhood SEP was associated with global cognition in adulthood (coefficient for parental education beyond high school vs. less than high school = 0.26, 95% confidence interval: 0.15, 0.37). This association was partially mediated through midlife SEP (indirect effect coefficient = 0.16, 95% confidence interval: 0.15, 0.18). Low SEP through the life course was associated with the lowest cognitive function. This study provides evidence that life-course SEP influences cognitive performance in adulthood.

Beyond borders: A commentary on the benefit of promoting immigrant populations in genome-wide association studies.

Immigrants are an important part of many high-income nations, in that they contribute to the sociocultural tapestry, economic well-being, and demographic diversity of their receiving countries and communities. Yet, genomic studies to date have generally focused on non-immigrant, European-ancestry populations. Although this approach has proven fruitful in discovering and validating genomic loci, within the context of racially/ethnically diverse countries like the United States-wherein half of immigrants hail from Latin America and another quarter from Asia-this approach is insufficient. There is a persistent diversity gap in genomic research in terms of both current samples and genome-wide association studies, meaning that the field's understanding of genetic architecture and gene-environmental interactions is being hampered. In this commentary, I provide motivating examples of recent research developments related to the following: (1) how the increased ancestral diversity, such as seen among Latin American immigrants, improves power to discover and document genomic loci, (2) informs how environmental factors, such as immigration-related exposures, interact with genotypes to influence phenotypes, and (3) how inclusion can be promoted through community-engaged research programs and policies. I conclude that greater inclusion of immigrants in genomic research can move the field forward toward novel discoveries and interventions to address racial/ethnic health disparities.

A Gene-Acculturation Study of Obesity Among US Hispanic/Latinos: The Hispanic Community Health Study/Study of Latinos.

OBJECTIVE: In the United States, Hispanic/Latino adults face a high burden of obesity; yet, not all individuals are equally affected, partly due in part to this ethnic group's marked sociocultural diversity. We sought to analyze the modification of body mass index (BMI) genetic effects in Hispanic/Latino adults by their level of acculturation, a complex biosocial phenomenon that remains understudied. METHODS: Among 11,747 Hispanic/Latinos adults in the Hispanic Community Health Study/Study of Latinos aged 18 to 76 years from four urban communities (2008-2011), we a) tested our hypothesis that the effect of a genetic risk score (GRS) for increased BMI may be exacerbated by higher levels of acculturation and b) examined if GRS acculturation interactions varied by gender or Hispanic/Latino background group. All genetic modeling controlled for relatedness, age, gender, principal components of ancestry, center, and complex study design within a generalized estimated equation framework. RESULTS: We observed a GRS increase of 0.34 kg/m 2 per risk allele in weighted mean BMI. The estimated main effect of GRS on BMI varied both across acculturation level and across gender. The difference between high and low acculturation ranged from 0.03 to 0.23 kg/m 2 per risk allele, but varied across acculturation measure and gender. CONCLUSIONS: These results suggest the presence of effect modification by acculturation, with stronger effects on BMI among highly acculturated individuals and female immigrants. Future studies of obesity in the Hispanic/Latino community should account for sociocultural environments and consider their intersection with gender to better target obesity interventions.

Erratum: Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium.

[This corrects the article DOI: 10.1016/j.xhgg.2022.100099.].

Genetic and stress influences on the prevalence of hypertension among hispanics/latinos in the hispanic community health study/study of latinos (HCHS/SOL).

PURPOSE: The current study examined the effects of chronic stress and a genetic risk score on the presence of hypertension and elevated systolic blood pressure and diastolic blood pressure among Hispanics/Latinos in the target population of Hispanic Community Health Study/Study of Latinos. MATERIALS AND METHODS: Of the participants (N = 11,623) assessed during two clinic visits (Visit 1 2008-2013 & Visit 2 2014-2018), we analysed data from 7,429 adults (50.4% female), aged 18-74, who were genotyped and responded to chronic stress questionnaires. We calculated an unweighted genetic risk score using blood pressure increasing single nucleotide polymorphisms (SNPs) found to be generalisable to Hispanics/Latinos (10 SNPs). Linear and logistic regression models were used to estimate associations between chronic stress and genetic risk score and their interaction, with prevalent Visit 2 SBP or DBP, and hypertension, respectively. Models accounted for sampling weights, stratification, and cluster design. RESULTS: Chronic stress (adjusted OR = 1.18, 95%CI:1.15,1.22) and hypertension genetic risk score (adjusted OR = 1.04, 95%CI:1.01,1.07) were significantly associated with prevalent hypertension, but there was no significant interaction between the chronic stress and genetic risk score on hypertension (p = .49). genetic risk score (b = .32, 95%CI:.08, .55, R2 = .02) and chronic stress (b = .45, 95%CI:.19, .72, R2 = .11) were related to DBP, with no significant interaction (p = .62). Genetic risk score (b = .42, 95%CI:.08, .76, R2 = .01) and chronic stress (b = .80, 95%CI:.34,1.26, R2 = .11) were also related to SBP, with no significant interaction (p = .51). CONCLUSION: Results demonstrate the utility of a genetic risk score for blood pressure and are consistent with literature suggesting chronic stress has a strong, direct association with elevated blood pressure among U.S. Hispanics/Latinos.

Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium.

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

Intergenerational educational mobility and type 2 diabetes in the Sacramento Area Latino Study on Aging.

PURPOSE: United States (US) Latinos have the lowest educational attainment of any US racial/ethnic group, which may contribute to their disparate burden of Type 2 Diabetes. Herein, we aimed to examine the association between intergenerational educational mobility and Type 2 Diabetes among US Latino adults. METHODS: We used data from the Niños Lifestyle and Diabetes Study (2013-2014) and the Sacramento Area Latino Study on Aging (1998-1999) to link 616 adult Latino children to their parents. Model-based standardization and robust Poisson regression were used to estimate the prevalence of prediabetes, Type 2 Diabetes, treatment and glycemic control, and describe their associations with intergenerational educational mobility. RESULTS: Adult children with stable high intergenerational educational attainment had a higher prevalence of prediabetes (Prevalence Ratio, PR=1.58; 95% Confidence Interval, CI=1.08, 2.34) and lower prevalence of Type 2 Diabetes (PR=0.64, CI=0.41, 0.99), as compared to those who experienced low educational attainment across generations. Downward mobility was associated with a higher prevalence of prediabetes (PR=1.54, CI=1.06, 2.23) and worse glycemic control (PR=2.20, CI=1.13, 4.30), and upward mobility was associated with a lower prevalence of Type 2 Diabetes (PR=0.39, CI=0.22, 0.70). CONCLUSIONS: Our findings from a predominantly Mexican-heritage community suggest that higher education across generations may buffer individuals from glycemic dysregulation. As such, higher education may be a promising public health target to address the rising burden of Type 2 Diabetes in the US.

Local-Level Immigration Enforcement and Risk of Pediatric Hospitalization for Ambulatory Care Sensitive Conditions.

Immigration enforcement may disrupt access to health care, potentially increasing hospitalizations for Ambulatory Care Sensitive Conditions (ACSC). We aimed to assess the effect of local-level 287(g) immigration enforcement on North Carolina pediatric ACSC hospitalizations. Pediatric (< 19 year) ACSC hospitalizations were identified based on ICD-9 codes. We compared ACSC hospitalizations pre and post 287(g) implementation using a difference-in-difference analysis of Fiscal Year (FY)2006-2009 data. We used multi-level models to assess the effects of 287(g) programs on ACSC hospitalizations during FY2011-2015. Difference-in-difference analyses showed that ACSC hospitalizations increased by more than 2.48% in the year following 287(g) implementation (95% CI: 0.99%, 3.97%). Among the counties that had ever implemented a 287(g) program, the ACSC-increasing effect of an active 287(g) program was greatest in counties with a shorter tenure of their 287(g) program and for Hispanic/Latino children/adolescents. Our findings underscore the importance of describing the effects of local-level immigration enforcement on pediatric access to care and potentially avoidable hospitalizations.

Findings from the Hispanic Community Health Study/Study of Latinos on the Importance of Sociocultural Environmental Interactors: Polygenic Risk Score-by-Immigration and Dietary Interactions.

Introduction: Hispanic/Latinos experience a disproportionate burden of obesity. Acculturation to US obesogenic diet and practices may lead to an exacerbation of innate genetic susceptibility. We examined the role of gene-environment interactions to better characterize the sociocultural environmental determinants and their genome-scale interactions, which may contribute to missing heritability of obesity. We utilized polygenic risk scores (PRSs) for body mass index (BMI) to perform analyses of PRS-by-acculturation and other environmental interactors among self-identified Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: PRSs were derived using genome-wide association study (GWAS) weights from a publicly available, large meta-analysis of European ancestry samples. Generalized linear models were run using a set of a priori acculturation-related and environmental factors measured at visit 1 (2008-2011) and visit 2 (2014-2016) in an analytic subsample of 8,109 unrelated individuals with genotypic, phenotypic, and complete case data at both visits. We evaluated continuous measures of BMI and waist-to-hip ratio. All models were weighted for complex sampling design, combined, and sex-stratified. Results: Overall, we observed a consistent increase of BMI with greater PRS across both visits. We found the best-fitting model adjusted for top five principal components of ancestry, sex, age, study site, Hispanic/Latino background genetic ancestry group, sociocultural factors and PRS interactions with age at immigration, years since first arrival to the United States (p < 0.0104), and healthy diet (p < 0.0036) and explained 16% of the variation in BMI. For every 1-SD increase in PRS, there was a corresponding 1.10 kg/m2 increase in BMI (p < 0.001). When these results were stratified by sex, we observed that this 1-SD effect of PRS on BMI was greater for women than men (1.45 vs. 0.79 kg/m2, p < 0.001). Discussion: We observe that age at immigration and the adoption of certain dietary patterns may play a significant role in modifying the effect of genetic risk on obesity. Careful consideration of sociocultural and immigration-related factors should be evaluated. The role of nongenetic factors, including the social environment, should not be overlooked when describing the performance of PRS or for promoting population health in understudied populations in genomics.

Demographic and sociocultural risk factors for adulthood weight gain in Hispanic/Latinos: results from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL).

BACKGROUND: United States (US) Hispanic/Latinos experience a disproportionate burden of obesity, which may in part be related to demographic or sociocultural factors, including acculturation to an US diet or inactive lifestyle. Therefore, we sought to describe the association between adulthood weight histories and demographic and sociocultural factors in a large diverse community-based cohort of US Hispanic/Latinos. METHODS: We estimated the effect of several factors on weight gain across adulthood, using multivariable linear mixed models to leverage 38,759 self-reported current body weights and weight histories recalled for 21, 45 and 65 years of age, from 15,203 adults at least 21 years of age at the baseline visit of the Hispanic Community Health Study/Study of Latinos (2008-2011). RESULTS: The average rate of weight gain was nearly 10 kg per decade in early adulthood, but slowed to < 5 kg a decade among individuals 60+ years of age. Birth cohort, gender, nativity or age at immigration, Hispanic/Latino background, and study site each significantly modified the form of the predicted adulthood weight trajectory. Among immigrants, weight gain during the 5 years post-migration was on average 0.88 kg (95% CI: 0.04, 1.72) greater than the weight gain during the 5 years prior. The rate of weight gain appeared to slow after 15 years post-migration. CONCLUSIONS: Using self-reported and weight history data in a diverse sample of US Hispanic/Latinos, we revealed that both demographic and sociocultural factors were associated with the patterning of adulthood weight gain in this sample. Given the steep rate of weight gain in this population and the fact that many Hispanic/Latinos living in the US immigrated as adults, efforts to promote weight maintenance across the life course, including after immigration, should be a top priority for promoting Hispanic/Latino health and addressing US health disparities more broadly.

Intergenerational Educational Attainment and Cardiometabolic Health in Latino Individuals Living in the United States.

OBJECTIVE: This study aimed to estimate the association between cycles of poverty, measured by intergenerational educational attainment (IEA), and the burden of obesity and metabolic dysfunction among Hispanic/Latino individuals in the United States. METHODS: This is a cross-sectional study utilizing data from 392 adults linked to 286 biologic parents from the Niños Lifestyle and Diabetes Study and the Sacramento Area Latino Study on Aging. The educational attainment of parents and offspring was dichotomized in order to categorize IEA. Outcomes included obesity and metabolic syndrome (MetS). Model-based standardization with population weights was used to compare obesity and MetS across generations, and Poisson regression was used to estimate prevalence ratios by IEA. RESULTS: A higher prevalence of obesity and MetS was observed in offspring (54% and 69%, respectively) compared with their parents (48% and 42%, respectively). Compared with stable-low IEA, any category with high offspring education was associated with lower obesity and MetS prevalence. The upwardly mobile group saw the greatest benefit; they were 38% (95% CI: 10%-57%) and 46% (95% CI: 21%-63%) less likely to have obesity or MetS. CONCLUSIONS: IEA strongly patterns cardiometabolic health among Hispanic/Latino individuals living in the United States, suggesting that promotion of higher education is associated with reductions in obesity and MetS, potentially benefitting future generations of this population.

Methylome-wide association study of central adiposity implicates genes involved in immune and endocrine systems.

Aim: We conducted a methylome-wide association study to examine associations between DNA methylation in whole blood and central adiposity and body fat distribution, measured as waist circumference, waist-to-hip ratio and waist-to-height ratio adjusted for body mass index, in 2684 African-American adults in the Atherosclerosis Risk in Communities study. Materials & methods: We validated significantly associated cytosine-phosphate-guanine methylation sites (CpGs) among adults using the Women's Health Initiative and Framingham Heart Study participants (combined n = 5743) and generalized associations in adolescents from The Raine Study (n = 820). Results & conclusion: We identified 11 CpGs that were robustly associated with one or more central adiposity trait in adults and two in adolescents, including CpG site associations near TXNIP, ADCY7, SREBF1 and RAP1GAP2 that had not previously been associated with obesity-related traits.

Adverse childhood experiences and lifetime adverse maternal outcomes (gestational diabetes and hypertensive disorders of pregnancy) in the Hispanic Community Health Study/Study of Latinos.

PURPOSE: Childhood adversity is associated with increased risk of adult disease, including type II diabetes and hypertension. However, little is known about potential associations between childhood adversity and adverse pregnancy outcomes. The goal of this study was to examine the relationship between adverse childhood experiences (ACEs) and ever experiencing gestational diabetes mellitus (GDM) or a hypertensive disorder of pregnancy (HDP) in a cohort of Hispanic or Latina women. METHODS: We analyzed data from 2319 women from the Hispanic Community Health Study/Study of Latinos who had ever given birth to a liveborn infant. We fit separate logistic regression models accounting for sample weights to examine the association between ACEs and risk of GDM and HDP adjusting for Hispanic/Latino background, age at immigration to the United States, and education. RESULTS: Women who reported four or more ACEs did not show increased odds of GDM or HDP compared with those who reported three or fewer (GDM adjusted odds ratio: 0.8 [0.5, 1.3]; HDP adjusted OR: 1.0 [0.7, 1.5]). CONCLUSIONS: Unlike previous research with majority non-Hispanic White cohorts, there was no association between ACEs and GDM or HDP. Future research should explore if this relationship varies by race/ethnicity in multiethnic cohorts.

Importance of Genetic Studies of Cardiometabolic Disease in Diverse Populations.

Genome-wide association studies have revolutionized our understanding of the genetic underpinnings of cardiometabolic disease. Yet, the inadequate representation of individuals of diverse ancestral backgrounds in these studies may undercut their ultimate potential for both public health and precision medicine. The goal of this review is to describe the imperativeness of studying the populations who are most affected by cardiometabolic disease, to the aim of better understanding the genetic underpinnings of the disease. We support this premise by describing the current variation in the global burden of cardiometabolic disease and emphasize the importance of building a globally and ancestrally representative genetics evidence base for the identification of population-specific variants, fine-mapping, and polygenic risk score estimation. We discuss the important ethical, legal, and social implications of increasing ancestral diversity in genetic studies of cardiometabolic disease and the challenges that arise from the (1) lack of diversity in current reference populations and available analytic samples and the (2) unequal generation of health-associated genomic data and their prediction accuracies. Despite these challenges, we conclude that additional, unprecedented opportunities lie ahead for public health genomics and the realization of precision medicine, provided that the gap in diversity can be systematically addressed. Achieving this goal will require concerted efforts by social, academic, professional and regulatory stakeholders and communities, and these efforts must be based on principles of equity and social justice.

A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity.

Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2-18 years old) and 15 599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry. In addition to observing 18 previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene, METTL15). The variant was nominally associated with only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than 10 single nucleotide polymorphisms (SNPs) (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.