Healthy Life In An Urban Setting Research Articles

Plasma sphingolipids mediate the association between gut microbiome composition and type 2 diabetes risk in the HELIUS cohort: a case-cohort study

IntroductionThe association between the gut microbiome and incident type 2 diabetes (T2D) is potentially partly mediated through sphingolipids, however these possible mediating mechanisms have not been investigated. We examined whether...

Differences in gut microbiota between Dutch and South-Asian Surinamese: potential implications for type 2 diabetes mellitus

Gut microbiota, or the collection of diverse microorganisms in a specific ecological niche, are known to significantly impact human health. Decreased gut microbiota production of short-chain fatty acids (SCFAs) has been implicated in type 2 diabetes mellitus (T2DM) disease progression. Most microbiome studies focus on ethnic majorities. This study aims to understand how the microbiome differs between an ethnic majority (the Dutch) and minority (the South-Asian Surinamese (SAS)) group with a lower and higher prevalence of T2DM, respectively. Microbiome data from the Healthy Life in an Urban Setting (HELIUS) cohort were used. Two age- and gender-matched groups were compared: the Dutch (n = 41) and SAS (n = 43). Microbial community compositions were generated via DADA2. Metrics of microbial diversity and similarity between groups were computed. Biomarker analyses were performed to determine discriminating taxa. Bacterial co-occurrence networks were constructed to examine ecological patterns. A tight microbiota cluster was observed in the Dutch women, which overlapped with some of the SAS microbiota. The Dutch gut contained a more interconnected microbial ecology, whereas the SAS network was dispersed, i.e., contained fewer inter-taxonomic correlational relationships. Bacteroides caccae, Butyricicoccus, Alistipes putredinis, Coprococcus comes, Odoribacter splanchnicus, and Lachnospira were enriched in the Dutch gut. Haemophilus, Bifidobacterium, and Anaerostipes hadrus discriminated the SAS gut. All but Lachnospira and certain strains of Haemophilus are known to produce SCFAs. The Dutch gut microbiome was distinguished from the SAS by diverse, differentially abundant SCFA-producing taxa with significant cooperation. The dynamic ecology observed in the Dutch was not detected in the SAS. Among several potential gut microbial biomarkers, Haemophilus parainfluenzae likely best characterizes the ethnic minority group, which is more predisposed to T2DM. The higher prevalence of T2DM in the SAS may be associated with the gut dysbiosis observed.

Ethnic Differences in Carotid Intima-Media Thickness and Plaque Presence: The HELIUS Study

Introduction: In the Netherlands, the prevalence of cardiovascular diseases (CVDs) is higher among South-Asian Surinamese and lower among Moroccans compared to the Dutch. Traditional risk factors for atherosclerotic CVD do not fully explain these disparities. We aimed to assess ethnic differences in plaque presence and carotid intima-media thickness (cIMT) and explore to what extent these differences are explained by traditional risk factors. Methods: We used cross-sectional data from a subgroup of participants enrolled in the multi-ethnic population-based Healthy Life in an Urban Setting (HELIUS) study who underwent carotid ultrasonography. Logistic and linear regression models were built to assess ethnic differences in plaque presence and cIMT with the Dutch population as reference. Additional models were created to adjust for socioeconomic status, body height, and cardiovascular risk factors. Results: Of the 3,022 participants, 1,183, 1,051, and 790 individuals were of Dutch, South-Asian Surinamese, and Moroccan descent, respectively. Mean age was 60.9 years (SD: 8.0), and 52.8% were female. Compared to the Dutch, we found lower odds for plaque presence in Moroccans (0.77, 95% CI: 0.62; 0.95) and no significant differences between the South-Asian Surinamese and Dutch population (0.91, 95% CI: 0.76; 1.10). After adjustment for CVD risk factors, we found a lower plaque presence in South-Asian Surinamese (0.63, 95% CI: 0.48; 0.82). In both Moroccan and South-Asian Surinamese individuals, adjustment for socioeconomic status did not materially change the results. cIMT was lower in South-Asian Surinamese compared to the Dutch (−17.9 μm, 95% CI: −27.9; −7.9) and partly explained by ethnic differences in the body height as South-Asian Surinamese individuals were, on average, shorter than the Dutch population. No differences in cIMT between Moroccans and Dutch were found. Conclusions: cIMT and plaque prevalence differ between ethnic groups independent of CVD risk. Lower plaque prevalence in Moroccans was partly attributable to a lower prevalence of traditional CVD risk factors, while body height was an important contributor to differences in cIMT in South Asians. This study emphasizes the need for ethnic-specific cut-off values for plaque presence and cIMT.

THE NATURAL COURSE OF HYPERTENSIVE PHENOTYPES OVER TIME – THE HELIUS STUDY

Objective: Hypertension can be classified into different phenotypes according to systolic and diastolic blood pressure (BP). We assessed the natural course of BP phenotypes over time in younger adults and identified risk factors predisposing to the development of sustained hypertension in a diverse population. Design and method: We used baseline and follow-up data from all participants aged below 40 years without antihypertensive medication at baseline from the ongoing multi-ethnic HEalthy LIFe in an Urban Setting (HELIUS) study. Participants were stratified according to baseline office BP: normotensive (NT; < 140/< 90 mmHg), isolated systolic hypertension (ISH; > = 140/< 90 mmHg), isolated diastolic hypertension (IDH; < 140/> = 90 mmHg) and combined systolic and diastolic hypertension (SDH; > = 140/> = 90 mmHg). Sankey diagrams were created stratified by sex to visualise change in phenotypes over time and risk of sustained hypertension (defined as BP > = 140/90 mmHg or use of antihypertensive medication) was assessed using logistic regression models adjusted for age, sex, ethnicity and follow-up time. In further adjusted models we added BMI, smoking, baseline eGFR, glucose, and total cholesterol levels to assess risk factors. Results: We included 2,818 participants aged 30.1 years (SD 6.0), 44% male, who attended the follow-up visit with a median follow-up time of 6.2 years (SD 1.1). Of all participants, 91.5% was normotensive at baseline, whereas 2.8%, 2.8% and 2.9% had ISH, IDH and SDH, respectively. In males the prevalence of ISH decreased over time, while in females the prevalence increased (figure). Compared to normotensive individuals, the adjusted odds ratios for developing sustained hypertension were 4.5 (95% CI 2.5 – 7.9) for ISH, 17.4 (95% CI 10.7 - 28.4) for IDH and 33.5, (95% CI 19.7 – 58.9) for SDH. Higher BMI was the most important predictor for development of sustained hypertension. Conclusions: Participants with SDH had the highest risk for developing sustained hypertension, followed by participants with IDH. The risk for sustained hypertension in individuals with ISH was much lower and differed between males and females, suggesting differences in pathophysiology and management.

ASSOCIATION BETWEEN SYSTOLIC BLOOD PRESSURE AND CHANGE IN EGFR OVER TIME IN A MULTI-ETHNIC COHORT: THE HELIUS STUDY

Objective: The assess the extent to which blood pressure relates to progression of CKD, among different ethnicities with disparate cardiorenal risk. We assessed the relationship between baseline systolic blood pressure (SBP) and change in renal function over time in a multi-ethnic population. Design and method: This analysis used baseline and follow-up data from 9 828 participants in the prospective Healthy Life in an Urban Setting (HELIUS) cohort study, a population-based study, including individuals of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan descent. Linear regression and interaction analysis were used to assess the association between baseline SBP and change in eGFR over time. Results: Overall eGFR decreased by -0.30 ml/min/1.73m2 (95%CI[-0.42, -0.19], p<0.001) per 10 mmHg increase in baseline SBP after 6.3 (SD 1.1) years of follow-up. This curve steepened from a SBP of 120 mmHg onwards to -0.44 ml/min/1.73m2 (95%CI[-0.61, -0.27], p<0.001) for every 10 mmHg increase in SBP. The association was significantly influenced by ethnicity (p<0.001), diabetes (p = 0.003) and albuminuria (p = 0.002), but not by age or sex. Individuals with albuminuria or diabetes had a more than 3 times larger SBP related eGFR decline compared to those without diabetes or albuminuria. Dutch, African Surinamese and Moroccan participants had a slightly steeper eGFR decline, but the direction of effect was consistent across all subgroups. Conclusions: Our findings confirm the relation between SBP and eGFR over time in different ethnic groups, steepening from a SBP of 120 mmHg onwards and may help to further guide strategies for preventing hypertension related CKD.

FHL2 Genetic Polymorphisms and Pro-Diabetogenic Lipid Profile in the Multiethnic HELIUS Cohort.

Type 2 diabetes mellitus (T2D) is a prevalent disease often accompanied by the occurrence of dyslipidemia. Four and a half LIM domains 2 (FHL2) is a scaffolding protein, whose involvement in metabolic disease has recently been demonstrated. The association of human FHL2 with T2D and dyslipidemia in a multiethnic setting is unknown. Therefore, we used the large multiethnic Amsterdam-based Healthy Life in an Urban Setting (HELIUS) cohort to investigate FHL2 genetic loci and their potential role in T2D and dyslipidemia. Baseline data of 10,056 participants from the HELIUS study were available for analysis. The HELIUS study contained individuals of European Dutch, South Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan descent living in Amsterdam and were randomly sampled from the municipality register. Nineteen FHL2 polymorphisms were genotyped, and associations with lipid panels and T2D status were investigated. We observed that seven FHL2 polymorphisms associated nominally with a pro-diabetogenic lipid profile including triglyceride (TG), high-density and low-density lipoprotein-cholesterol (HDL-C and LDL-C), and total cholesterol (TC) concentrations, but not with blood glucose concentrations or T2D status in the complete HELIUS cohort upon correcting for age, gender, BMI, and ancestry. Upon stratifying for ethnicity, we observed that only two of the nominally significant associations passed multiple testing adjustments, namely, the association of rs4640402 with increased TG and rs880427 with decreased HDL-C concentrations in the Ghanaian population. Our results highlight the effect of ethnicity on pro-diabetogenic selected lipid biomarkers within the HELIUS cohort, as well as the need for more large multiethnic cohort studies.

Noninvasive tests for nonalcoholic fatty liver disease in a multi-ethnic population: The HELIUS study.

Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence and severity globally, prompting noninvasive testing, yet limited data exist on noninvasive liver tests (NITs) including transient elastography (TE) in ethnically diverse populations. Therefore, we studied prevalence and ethnic differences in NAFLD with NITs in the multi-ethnic HEalthy Life In an Urban Setting (HELIUS) cohort. NITs of liver steatosis (Fatty Liver Index [FLI]) and fibrosis (Fibrosis-4 index [FIB-4], and aspartate aminotransferase-to-platelet ratio [APRI]) were assessed in 10,007 participants. A subpopulation of 399 participants, selected on high-risk criteria for NAFLD (obesity, type 2 diabetes mellitus [T2DM], and/or elevated NITs), was examined with TE. FLI was ≥60 in 27.3% of 10,007 participants, indicating steatosis. Most participants (71.8%) had FIB-4 < 1.30, excluding advanced liver fibrosis, and 1.1% (n=113) had high FIB-4 (FIB-4 ≥ 2.67), indicating likely advanced liver fibrosis. In the TE subpopulation, 37.8% and 17.3% had steatosis and fibrosis (continuation attenuation parameter [CAP] ≥ 280 dB/m, liver stiffness measurement [LSM] ≥ 7.0 kPa, respectively). Turkish participants had highest adjusted odds ratio (OR) for elevated LSM (1.72, 95% confidence interval [CI] 0.59-5.01) and Ghanaians the lowest (0.24, 95% CI 0.09-0.65). Ghanaians had lowest adjusted OR for elevated CAP: 0.18 (95% CI 0.09-0.37). In diabetics, CAP and LSM were 17.6% and 14.6% higher than in nondiabetics, respectively. Correlations of FIB-4 and APRI with LSM were absent and weak. Conclusion : Liver steatosis proxy FLI was elevated in 27.3% of this multi-ethnic population. In Turkish background and in those with T2DM, proxies for steatosis and fibrosis were high, whereas in Ghanaian background, NITs were generally low. Together, this warrants awareness for NAFLD among high-risk populations, taking ethnic background into account. The absence of clear correlation between FIB-4 and APRI with LSM questions the accuracy of these fibrosis NITs to detect advanced fibrosis in the general population.

Lifetime prevalence and correlates of syncope in five ancestry groups. The HELIUS study.

To explore the lifetime prevalence and correlates of syncope in the general population. Through stratified random sampling, we included 14,937 White-European, Asian, Turkish, Moroccan, and West-African ancestry adults (18-70 y) in the cross-sectional Healthy Life in an Urban Setting (HELIUS) population study. We assessed syncope history by ancestry, and the potential correlates body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP), resting plasma activity of creatine kinase (CK), the ATP-generating enzyme that facilitates cardiovascular contractility and sodium retention, and in a subgroup, supine cardiac contractility (dP/dt), cardiac output (CO) and systemic vascular resistance (SVR). Mean age of the participants (39% men) was 43.3 y (SD12.9). Lifetime prevalence of syncope in women/men was respectively (%), White-European 42/24; Asian 34/19; Moroccan 32/16; Turkish 30/17; and West-African 20/14. Mean age at first syncope was 24 y (SD13). Participants with syncope history had lower SBP, DBP, BMI, CK, and modestly lower dP/dt and CO, but not SVR. In multivariable regression analysis, male sex (OR 0.52 [0.48 to 0.57]), West-African ancestry (0.59 [0.54 to 0.65]), and CK (0.56 [0.46 to 0.69]/log CK increase) were negatively associated with syncope. This study indicates that West-African ancestry, male sex, and high activity of the pressor enzyme CK are associated with lower syncope prevalence. These findings may inform further studies on the hemodynamics of syncope.

Gut microbiome associations with host genotype vary across ethnicities and potentially influence cardiometabolic traits

Previous studies in mainly European populations have reported that the gut microbiome composition is associated with the human genome. However, the genotype-microbiome interaction in different ethnicities is largely unknown. We performed a large fecal microbiome genome-wide association study of a single multiethnic cohort, the Healthy Life in an Urban Setting (HELIUS) cohort (N= 4,117). Mendelian randomization was performed using the multiethnic Pan-UK Biobank (N= 460,000) to dissect potential causality. We identified ethnicity-specific associations between host genomes and gut microbiota. Certain microbes were associated with genotype in multiple ethnicities. Several of the microbe-associated loci were found to be related to immune functions, interact with glutamate and the mucus layer, or be expressed in the gut or brain. Additionally, we found that gut microbes potentially influence cardiometabolic health factors such as BMI, cholesterol, and blood pressure. This provides insight into the relationship of ethnicity and gut microbiota and into the possible causal effects of gut microbes on cardiometabolic traits.

PRELIMINARY REPORT: BLOOD PRESSURE TRAJECTORIES OVER TIME IN A MULTI-ETHNIC POPULATION

Objective: Objective: Hypertension remains the leading cause of cardiovascular diseases worldwide. Major interethnic differences in the prevalence of hypertension exist. Exploring blood pressure (BP) levels in a large prospective multi-ethnic population provides insight in interethnic differences in blood pressure trajectories across the life course. Design and method: Design and method: We examined BP course over time in participants from the HEalthy Life in an Urban Setting (HELIUS) study. Participants aged 18–70 years from Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin with BP data at baseline and follow-up were included. BP levels were corrected for the use of antihypertensive medication. BP change over time was expressed as delta systolic blood pressure (delta SBP) and delta diastolic blood pressure (delta DBP). Multivariate regression analyses were performed to assess the association between ethnicity and BP levels at follow-up, with correction for sex, age, follow-up time, change of BMI and blood pressure levels at baseline. Results: Results: In total 8.053 participants (mean age 46.2 (12.4) years, 43.8% female) were included. Median follow-up time was 6.2 (5.3–7.1) years. Overall there was a slight increase in SBP over time (129.41 mmHg at baseline vs. 129.87 at follow-up), while diastolic blood pressure levels tended to decrease (delta DBP = -0.59 mmHg) (Figure 1). The highest SBP increase was found in the Ghanaian population (+1.84 mmHg), while the largest decrease was observed in in the Dutch population (-0.28 mmHg). The lowest DBP decrease was found in the Ghanaian population (-0.02 mmHg) and the highest decrease in the South-Asian Surinamese population (-1.31 mmHg). Multivariable regression analysis showed a strong association between ethnicity and SBP at follow-up, especially for the Ghanaian population (β = 5.51 (95%CI 4.42 – 6.61), p = 2.2e-16) compared to the Dutch reference population. For DBP these interethnic differences were also present, but less pronounced. Conclusions: Conclusions: Major interethnic differences in the course of blood pressure over time were found, with substantially higher SBP levels in the Ghanaian population compared to the reference Dutch population.

ASSOCIATION BETWEEN THE REFLECTION MAGNITUDE AND BLOOD-PRESSURE IN A MULTI-ETHNIC COHORT: THE HELIUS STUDY

Objective: The reflection magnitude (RM), the ratio of the amplitudes of the backward and forward central arterial pressure waves, has been shown to be predictive for future cardiovascular events, but the association between blood pressure (BP) and RM remains unknown. We aimed to assess the association between RM, BP and hypertension in a large multi-ethnic population-based cohort study. Design and method: We assessed RM in 10 195 individuals of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin aged between 18–70 years (54.2% female) participating in the HEalthy Life in an Urban Setting (HELIUS) study. To determine RM, central arterial pressure and flow were reconstructed from non-invasive finger BP measurements using a generalized transfer function and Windkessel model, whereafter wave separation was performed (Fig 1, panel A &amp; B). Hypertension was defined based on office-BP and use of BP lowering medication. Associations between RM and systolic- and diastolic BP, hypertension, and hypertension mediated end-organ damage were assessed using regression models with correction for age, height, ethnicity and an interaction term for sex. Results: Mean RM was 62.5% (SD 8.0) in men and 63.8% (SD 8.1) in women. For every 10 mmHg increase in systolic BP, RM increased linearly by 1.35 (95% CI 1.23–1.46) from 120 mmHg onwards, while for every 10 mmHg increase in diastolic BP above 80 mmHg RM increased by 1.99 (95% CI 1.61 – 2.38) (Fig 1, panel C &amp; D). RM was 2.40 (95% CI 2.04–2.76) higher in hypertensive men and 3.82 (95% CI 3.46–4.19) higher in hypertensive women compared to normotensive men and women. RM was 1.64 (95% CI 1.09–2.20) and 0.94 (95% CI 0.37–1.52) higher in hypertensive men and women with ECG-based left ventricular hypertrophy or increased albuminuria compared to hypertensive men and women without hypertensive organ damage. Following correction for height ethnic and sex differences in RM were attenuated, however the relation with BP did not change. Conclusions: Hypertension is associated with a higher RM in men and women of different ethnic origins, and may, in part, explain disparities in hypertension associated cardiovascular risk.

Protocol Standardization of Microbiome Studies—Daunting but Necessary

Protocol Standardization of Microbiome Studies—Daunting but Necessary

The association between socioeconomic status and prevalence, awareness, treatment and control of hypertension in different ethnic groups: the Healthy Life in an Urban Setting study.

Socioeconomic status (SES) and ethnicity are both important determinants of hypertension prevalence and control rates but their separate contribution is unknown. We assessed the association of SES with hypertension prevalence, awareness, treatment and control, and whether this differs between ethnic groups. We used baseline data from the Healthy Life in an Urban Setting (HELIUS) study, a multiethnic population-based cohort study, including 18 106 participants (84% of the total cohort) of Dutch (n = 4262), African Surinamese (n = 3732), Moroccan (n = 2902), Turkish (n = 2694), South-Asian Surinamese (n = 2664) and Ghanaian (n = 1947) descent with data on SES and hypertension status. Regardless of ethnicity, lower SES was associated with higher hypertension prevalence, especially in participants with no education compared with those with higher levels of education [OR 2.29 (2.05-2.56)]. There was an inverse association between SES and hypertension treatment with the strongest association for lower compared with higher educated participants [OR 1.63 (1.39-1.90)]. In addition, lower SES was associated with lower hypertension control with the strongest association for participants with the lowest compared with the highest occupational level [OR 0.76 (0.60-0.95)]. The association between educational level and treatment but not the other SES- or hypertension-indicators, was influenced by ethnicity, with lower educated Dutch and African Surinamese having higher ORs for hypertensive treatment [Dutch OR 1.98 (1.43-2.76); African Surinamese OR 1.44 (1.10-1.89)]. SES, in particular education, impacts hypertension treatment in the Netherlands, whereas the association of specific SES parameters with hypertension indicators differ across ethnic groups. Further exploration is needed on how sociocultural beliefs and behaviours may differentially affect blood pressure control across ethnic minority populations.

The association between child maltreatment and problematic alcohol use in adulthood in a large multi-ethnic cohort: the HELIUS study.

There is evidence that child maltreatment is associated with problematic alcohol use later in life. However, previous epidemiological studies that have examined the link between child maltreatment and adult problematic alcohol use have not considered ethnic differences. Therefore, the purpose of the current study was to investigate the relationship between child maltreatment and adult problematic alcohol use among six ethnic groups in the Netherlands, in a large, urban sample. This study used baseline data from the Healthy Life in an Urban Setting (HELIUS) study: a large-scale, multi-ethnic prospective cohort study conducted in Amsterdam, the Netherlands. Child maltreatment, current problematic alcohol use and several potential confounders (e.g. parental alcohol use) were assessed in participants (N = 23 356) of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin. With logistic regression analyses, we examined effect modification by ethnicity on the association between child maltreatment and problematic alcohol use. Furthermore, we explored effect modification by ethnicity for specific types of child maltreatment, namely: physical, sexual and psychological abuse and emotional neglect. Effect modification by ethnicity was present. Stronger associations between child maltreatment and problematic alcohol use were found in all ethnic minority groups compared to the Dutch reference group. Particularly strong associations between all four types of child maltreatment and alcohol use problems were found for the Moroccan origin group. This study adds to a growing body of evidence that child maltreatment is associated with problematic alcohol use in adulthood. In addition, our findings indicate that ethnicity impacts this relationship. Although problematic alcohol use was more prevalent in the Dutch origin group, associations with child maltreatment were stronger in ethnic minority groups. Future studies on child maltreatment and alcohol use problems should also examine ethnic disparities and should further unravel how these disparities can be explained.

Physical Activity and Dietary Composition Relate to Differences in Gut Microbial Patterns in a Multi-Ethnic Cohort-The HELIUS Study.

Physical activity (PA) at recommended levels contributes to the prevention of non-communicable diseases, such as atherosclerotic cardiovascular disease (asCVD) and type 2 diabetes mellitus (T2DM). Since the composition of the gut microbiota is strongly intertwined with dietary intake, the specific effect of exercise on the gut microbiota is not known. Moreover, multiple other factors, such as ethnicity, influence the composition of the gut microbiota, and this may be derived by distinct diet as well as PA patterns. Here we aim to untangle the associations between PA and the gut microbiota in a sample (n = 1334) from the Healthy Life In an Urban Setting (HELIUS) multi-ethnic cohort. The associations of different food groups and gut microbiota were also analyzed. PA was monitored using subjective (n = 1309) and objective (n = 162) methods, and dietary intake was assessed with ethnic-specific food frequency questionnaire (FFQ). The gut microbiota was profiled using 16S rRNA gene amplicon sequencing, and the functional composition was generated with the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2). Associations were assessed using multivariable and machine learning models. In this cohort, a distinct gut microbiota composition was associated with meeting the Dutch PA norm as well as with dietary intake, e.g., grains. PA related parameters such as muscle strength and calf circumference correlated with gut microbiota diversity. Furthermore, gut microbial functionality differed between active and sedentary groups. Differential representation of ethnicities in active and sedentary groups in both monitor methods hampered the detection of ethnic-specific effects. In conclusion, both PA and dietary intake were associated with gut microbiota composition in our multi-ethnic cohort. Future studies should further elucidate the role of ethnicity and diet in this association.

A Genetic Map of the Modern Urban Society of Amsterdam.

Genetic differences between individuals underlie susceptibility to many diseases. Genome-wide association studies (GWAS) have discovered many susceptibility genes but were often limited to cohorts of predominantly European ancestry. Genetic diversity between individuals due to different ancestries and evolutionary histories shows that this approach has limitations. In order to gain a better understanding of the associated genetic variation, we need a more global genomics approach including a greater diversity. Here, we introduce the Healthy Life in an Urban Setting (HELIUS) cohort. The HELIUS cohort consists of participants living in Amsterdam, with a level of diversity that reflects the Dutch colonial and recent migration past. The current study includes 10,283 participants with genetic data available from seven groups of inhabitants, namely, Dutch, African Surinamese, South-Asian Surinamese, Turkish, Moroccan, Ghanaian, and Javanese Surinamese. First, we describe the genetic variation and admixture within the HELIUS cohort. Second, we show the challenges during imputation when having a genetically diverse cohort. Third, we conduct a body mass index (BMI) and height GWAS where we investigate the effects of a joint analysis of the entire cohort and a meta-analysis approach for the different subgroups. Finally, we construct polygenic scores for BMI and height and compare their predictive power across the different ethnic groups. Overall, we give a comprehensive overview of a genetically diverse cohort from Amsterdam. Our study emphasizes the importance of a less biased and more realistic representation of urban populations for mapping genetic associations with complex traits and disease risk for all.

Lifetime prevalence of syncope: the HELIUS study

Abstract Background Syncope is a common presentation to emergency departments. Cardiovascular risk differs markedly among ancestry groups, but data on syncope are scarce. Fundamental understanding of the determinants of syncope in the population might aid in the risk stratification of syncope in acute settings. Purpose To assess lifetime prevalence of syncope and its determinants in the general population. Methods We included 14937 adults (18–70 y) randomly sampled in the cross-sectional Healthy Life in an Urban Setting (HELIUS) population study, stratified by White-European, Asian, Turkish, Moroccan, and West-African ancestry. We assessed syncope history, body mass index (BMI), blood pressure (BP), supine stroke volume (SV), cardiac contractility (dP/dt), cardiac output (CO), systemic vascular resistance (SVR), and resting plasma activity of CK, an ATP-generating enzyme that facilitates cardiovascular contractility and sodium retention, counteracting hypotensive susceptibility. Results Mean age of the participants (39% men) was 43.3 y (SD 12.9). Lifetime prevalence of syncope was significantly higher in women (31%) vs. men (18%); and in White-European (34%) and other ancestries (25 to 28%), vs. West-African ancestry (19%) (Figure 1). Mean age at first syncope was 24 y (SD 13). Participants without syncope history had higher BP (systolic, +29% SD), BMI (+17% SD), CK (+31% SD) (Figure 1), modestly higher SV, dP/dt, and CO (+6 to 8% SD), and more diabetes (5.2 vs 3.6%). The main protective predictors of syncope were West-African ancestry (0.59 [0.54 to 0.65]), male sex (0.52 [0.48 to 0.57]), and CK (0.56 [0.46 to 0.69]/log CK increase), with high CK in men and West-African ancestry largely explaining the low syncope prevalence in these groups. Conclusion To our knowledge the first population study on syncope by ancestry indicates that the lifetime prevalence is high in White-European women, and low in person of African ancestry. The inverse association of syncope with the pressor enzyme CK needs further study. Funding Acknowledgement Type of funding sources: None. Figure 1. Syncope by Sex, Ancestry, and CK

A Bayesian Negative Binomial Hierarchical Model for Identifying Diet-Gut Microbiome Associations.

The human gut microbiota composition plays an important role in human health. Long-term diet intervention may shape human gut microbiome. Therefore, many studies focus on discovering links between long-term diets and gut microbiota composition. This study aimed to incorporate the phylogenetic relationships between the operational taxonomic units (OTUs) into the diet-microbe association analysis, using a Bayesian hierarchical negative binomial (NB) model. We regularized the dispersion parameter of the negative binomial distribution by assuming a mean-dispersion association. A simulation study showed that, if over-dispersion is present in the microbiome data, our approach performed better in terms of mean squared error (MSE) of the slope-estimates compared to the standard NB regression model or a Bayesian hierarchical NB model without including the phylogenetic relationships. Data of the Healthy Life in an Urban Setting (HELIUS) study showed that for some phylogenetic families the (posterior) variances of the slope-estimates were decreasing when including the phylogenetic relationships into the analyses. In contrast, when OTUs of the same family were not similarly affected by the food item, some bias was introduced, leading to larger (posterior) variances of the slope-estimates. Overall, the Bayesian hierarchical NB model, with a dependency between the mean and dispersion parameters, proved to be a robust method for analyzing diet-microbe associations.

Differences in Body Composition Convey a Similar Risk of Type 2 Diabetes Among Different Ethnic Groups With Disparate Cardiometabolic Risk-The HELIUS Study.

Studies have shown a disparate association between body composition and the risk of type 2 diabetes. We assessed whether associations between differences in body composition and type 2 diabetes vary among ethnic groups with disparate cardiometabolic risk. We used data from the Healthy Life in an Urban Setting (HELIUS) study, including individuals aged 18-70 years of African Surinamese (n = 3,997), South Asian Surinamese (n = 2,956), Turkish (n = 3,546), Moroccan (n = 3,850), Ghanaian (n = 2,271), and Dutch (n = 4,452) origin living in Amsterdam. Type 2 diabetes was defined using the World Health Organization criteria. Logistic regression was used to assess the relation between body composition and type 2 diabetes. Waist-to-hip ratio (WHR), waist circumference, BMI, and body fat percentage by bioelectrical impedance were used to estimate body composition. Per unit change in BMI, only Ghanaian (odds ratio [OR] 0.94 [95% CI 0.89-0.99]) and Moroccan (0.94 [0.89-0.99]) women had a smaller increase in type 2 diabetes compared with the Dutch population, whereas the ORs for body fat percentage were 0.94 (0.89-1.00) for Ghanaian, 0.93 (0.88-0.99) for Moroccan, and 0.95 (0.90-1.00) for South Asian Surinamese women. There was no interaction between WHR and ethnicity on the risk of type 2 diabetes, and there were no differences in men. WHR had the highest precision in predicting type 2 diabetes in both men (C statistic = 0.78) and women (C statistic = 0.81). The association between differences in body composition and type 2 diabetes is roughly the same in all ethnic groups. WHR seems the most reliable and consistent predictor of type 2 diabetes regardless of ethnic background.

Associations between macrovascular and renal microvascular dysfunction in type 2 diabetes and non-diabetes: the HELIUS study

BackgroundAlthough the associations between measures of macrovascular and microvascular dysfunctions are well characterized in diabetes, there is limited data on these associations in individuals without diabetes. We compared the associations between macrovascular dysfunction and renal microvascular dysfunction in individuals with type 2 diabetes (T2D) and without diabetes. MethodsCross-sectional analyses of baseline data from the multiethnic Healthy Life in an Urban Setting (HELIUS) study (Amsterdam, the Netherlands), including 986 participants with T2D and 7680 participants without diabetes were done. Logistic regression analyses were used to examine the associations between macrovascular dysfunction [aortic stiffness, coronary artery disease (CAD), peripheral artery disease (PAD), and stroke] and renal microvascular dysfunction [albuminuria] with adjustments for age, sex, ethnicity, waist-to-hip ratio, systolic blood pressure, LDL-cholesterol, and smoking (and HbA1c and diabetes duration for the T2D group). ResultsIn the fully adjusted models, aortic stiffness was associated with albuminuria in individuals with T2D [OR 2.55; 95% CI,1.30–4.98], but not without diabetes [0.96; 0.63–1.45]; stroke was associated with albuminuria in T2D [2.40;1.10–5.25], but not in non-diabetes [1.39;0.83–2.33]. In age-sex adjusted models, CAD was associated with albuminuria in T2D [1.65;1.09–2.50] and in non-diabetes [1.56;1.13–2.15]; the associations were no longer significant in the fully adjusted model. There were no associations between PAD and albuminuria in T2D and non-diabetes. ConclusionsOur study shows important differences in the associations between measures of macrovascular and renal microvascular dysfunction in T2D and non-diabetes. These findings provide opportunities for future research aimed at prevention and treatment strategies for individuals with vascular dysfunction.