International Migration and Cardiovascular Health: Unraveling the Disease Burden Among Migrants to North America and Europe.

Europe and North America are the 2 largest recipients of international migrants from low-resource regions in the world. Here, large differences in cardiovascular disease (CVD) morbidity and death exist between migrants and the host populations. This review discusses the CVD burden and its most important contributors among the largest migrant groups in Europe and North America as well as the consequences of migration to high-income countries on CVD diagnosis and therapy. The available evidence indicates that migrants in Europe and North America generally have a higher CVD risk compared with the host populations. Cardiometabolic, behavioral, and psychosocial factors are important contributors to their increased CVD risk. However, despite these common denominators, there are important ethnic differences in the propensity to develop CVD that relate to pre- and postmigration factors, such as socioeconomic status, cultural factors, lifestyle, psychosocial stress, access to health care and health care usage. Some of these pre- and postmigration environmental factors may interact with genetic (epigenetics) and microbial factors, which further influence their CVD risk. The limited number of prospective cohorts and clinical trials in migrant populations remains an important culprit for better understanding pathophysiological mechanism driving health differences and for developing ethnic-specific CVD risk prediction and care. Only by improved understanding of the complex interaction among human biology, migration-related factors, and sociocultural determinants of health influencing CVD risk will we be able to mitigate these differences and truly make inclusive personalized treatment possible.

SARS-CoV-2 vaccination uptake in six ethnic groups living in Amsterdam, the Netherlands: A registry-based study within the HELIUS cohort.

OBJECTIVE: Ethnic minority groups have experienced a disproportionate burden of COVID-19, and should therefore be especially encouraged to receive SARS-CoV-2 vaccination. This study compared first-dose uptake of the primary SARS-CoV-2 vaccination series across six ethnic groups in Amsterdam, the Netherlands in 2021. METHODS: We analyzed data from participants of the population-based HELIUS cohort. We linked their data to the SARS-CoV-2 vaccination registry data of the Public Health Service of Amsterdam. We included registry data from January 6, 2021 (the start of the Dutch vaccination campaign) until September 6, 2021 (a date by which all adults in the Netherlands could have received one or two vaccine doses). SARS-CoV-2 vaccination uptake was defined as having received at least one vaccine dose of the primary vaccination series. We examined the association between ethnicity and vaccination uptake using multivariable logistic regression, while accounting for the age and sex distribution of ethnic groups in Amsterdam. RESULTS: We included 19,006 participants (median age 53 years [interquartile range 41-62], 57% female). SARS-CoV-2 vaccination uptake was highest in the South-Asian Surinamese group (60.3%, 95%CI = 58.2-62.3%), followed by the Dutch (59.6%, 95%CI = 58.0-61.1%), Ghanaian (54.1%, 95%CI = 51.7-56.5%), Turkish (47.7%, 95%CI = 45.9-49.6%), African Surinamese (43.0%, 95%CI = 41.2-44.7%), and Moroccan (35.8%, 95%CI = 34.1-37.5%) groups. After adjusting for age, sex, perceived social support, and presence of relevant comorbidities, participants of African Surinamese, Ghanaian, Turkish and Moroccan origin were significantly less likely to be vaccinated than those of Dutch origin. CONCLUSIONS: Prevention strategies should continue tailoring to specific ethnic groups to encourage vaccination uptake and reduce barriers to vaccination.

Associations between epigenome-wide DNA methylation and height-related traits among Sub-Saharan Africans: the RODAM study.

Human height and related traits are highly complex, and extensively research has shown that these traits are determined by both genetic and environmental factors. Such factors may partially affect these traits through epigenetic programing. Epigenetic programing is dynamic and plays an important role in controlling gene expression and cell differentiation during (early) development. DNA methylation (DNAm) is the most commonly studied epigenetic feature. In this study we conducted an epigenome-wide DNAm association analysis on height-related traits in a Sub-Saharan African population, in order to detect DNAm biomarkers across four height-related traits. DNAm profiles were acquired in whole blood samples of 704 Ghanaians, sourced from the Research on Obesity and Diabetes among African Migrants study, using the Illumina Infinium HumanMethylation450 BeadChip. Linear models were fitted to detect differentially methylated positions (DMPs) and regions (DMRs) associated with height, leg-to-height ratio (LHR), leg length, and sitting height. No epigenome-wide significant DMPs were recorded. However we did observe among our top DMPs five informative probes associated with the height-related traits: cg26905768 (leg length), cg13268132 (leg length), cg19776793 (height), cg23072383 (LHR), and cg24625894 (sitting height). All five DMPs are annotated to genes whose functions were linked to bone cell regulation and development. DMR analysis identified overlapping DMRs within the gene body of HLA-DPB1 gene, and the HOXA gene cluster. In this first epigenome-wide association studies of these traits, our findings suggest DNAm associations with height-related heights, and might influence development and maintenance of these traits. Further studies are needed to replicate our findings, and to elucidate the molecular mechanism underlying human height-related traits.

A multilevel and multicenter assessment of health care system capacity to manage cardiovascular diseases in Africa: a baseline study of the Ghana Heart Initiative.

INTRODUCTION: Cardiovascular diseases (CVD) remain the leading cause of death worldwide, with over 70% of these deaths occurring in low- and middle-income regions such as Africa. However, most countries in Africa do not have the capacity to manage CVD. The Ghana Heart Initiative has been an ongoing national program since 2018, aimed at improving CVD care and thus reducing the death rates of these diseases in Ghana. This study therefore aimed at assessing the impact of this initiative by identifying, at baseline, the gaps in the management of CVDs within the health system to develop robust measures to bolster CVD management and care in Ghana. METHODS: This study employed a cross-sectional study design and was conducted from November 2019 to March 2020 in 44 health facilities in the Greater Accra region. The assessment covered CVD management, equipment availability, knowledge of health workers in CVD and others including the CVD management support system, availability of CVD management guidelines and CVD/NCD indicators in the District Health Information Management System (DHIMS2). RESULTS: The baseline data showed a total of 85,612 outpatient attendants over the period in the study facilities, 70% were women and 364(0.4%) were newly diagnosed with hypertension. A total of 83% of the newly diagnosed hypertensives were put on treatment, 56.3% (171) continued treatment during the study period and less than 10% (5%) had their blood pressure controlled at the end of the study (in March 2020). Other gaps identified included suboptimal health worker knowledge in CVD management (mean score of 69.0 ± 13.0, p < 0.05), lack of equipment for prompt CVD emergency diagnosis, poor management and monitoring of CVD care across all levels of health care, lack of standardized protocol on CVD management, and limited number of indicators on CVD in the National Database (i.e., DHIMS2) for CVD monitoring. CONCLUSION: This study shows that there are gaps in CVD care and therefore, there is a need to address such gaps to improve the capacity of the health system to effectively manage CVDs in Ghana.

Relative contributions of pre-pandemic factors and intra-pandemic activities to differential COVID-19 risk among migrant and non-migrant populations in the Netherlands: lessons for future pandemic preparedness.

BACKGROUND: Although risk factors for differences in SARS-CoV-2 infections between migrant and non-migrant populations in high income countries have been identified, their relative contributions to these SARS-CoV-2 infections, which could aid in the preparation for future viral pandemics, remain unknown. We investigated the relative contributions of pre-pandemic factors and intra-pandemic activities to differential SARS-CoV-2 infections in the Netherlands by migration background (Dutch, African Surinamese, South-Asian Surinamese, Ghanaians, Turkish, and Moroccan origin). METHODS: We utilized pre-pandemic (2011-2015) and intra-pandemic (2020-2021) data from the HELIUS cohort, linked to SARS-CoV-2 PCR test results from Public Health Service of Amsterdam (GGD Amsterdam). Pre-pandemic factors included socio-demographic, medical, and lifestyle factors. Intra-pandemic activities included COVID-19 risk aggravating and mitigating activities such as physical distancing, use of face masks, and other similar activities. We calculated prevalence ratios (PRs) in the HELIUS population that was merged with GGD Amsterdam PCR test data using robust Poisson regression (SARS-CoV-2 PCR test result as outcome, migration background as predictor). We then obtained the distribution of migrant and non-migrant populations in Amsterdam as of January 2021 from Statistics Netherlands. The migrant populations included people who have migrated themselves as well as their offspring. We used PRs and the population distributions to calculate population attributable fractions (PAFs) using the standard formula. We used age and sex adjusted models to introduce pre-pandemic factors and intra-pandemic activities, noting the relative changes in PAFs. RESULTS: From 20,359 eligible HELIUS participants, 8,595 were linked to GGD Amsterdam PCR test data and included in the study. Pre-pandemic socio-demographic factors (especially education, occupation, and household size) resulted in the largest changes in PAFs when introduced in age and sex adjusted models (up to 45%), followed by pre-pandemic lifestyle factors (up to 23%, especially alcohol consumption). Intra-pandemic activities resulted in the least changes in PAFs when introduced in age and sex adjusted models (up to 16%). CONCLUSION: Interventions that target pre-pandemic socio-economic status and other drivers of health inequalities between migrant and non-migrant populations are urgently needed at present to better prevent infection disparities in future viral pandemics.

Differences in incidence, nature of symptoms, and duration of long COVID among hospitalised migrant and non-migrant patients in the Netherlands: a retrospective cohort study.

Background: Comprehensive data on long COVID across ethnic and migrant groups are lacking. We investigated incidence, nature of symptoms, clinical predictors, and duration of long COVID among COVID-19 hospitalised patients in the Netherlands by migration background (Dutch, Turkish, Moroccan, and Surinamese origin, Others). Methods: We used COVID-19 admissions and follow up data (January 2021-July 2022) from Amsterdam University Medical Centers. We calculated long COVID incidence proportions per NICE guidelines by migration background and assessed for clinical predictors via robust Poisson regressions. We then examined associations between migration background and long COVID using robust Poisson regressions and adjusted for derived clinical predictors, and other biologically relevant factors. We also assessed long COVID symptom persistence at one-year post-discharge. Findings: 1886 patients were included. 483 patients had long COVID (26%, 95% CI 24-28%) at 12 weeks post-discharge. Symptoms like dizziness, joint pain, insomnia, and headache varied by migration background. Clinical predictors of long COVID were female sex, hospital admission duration, intensive care unit admission, and receiving oxygen, or corticosteroid therapy. Long COVID risk was higher among patients with migration background than Dutch origin patients after adjustments for derived clinical predictors, age, smoking, vaccination status, comorbidities and remdesivir treatment. Only 14% of long COVID symptoms persisted at one-year post-discharge. Interpretation: There are significant differences in occurrence, nature of symptoms, and duration of long COVID by migration background. Studies assessing the spectrum of functional limitation and access to post-COVID healthcare are needed to help plan for appropriate and accessible healthcare interventions. Funding: The Amsterdam UMC COVID-19 biobank is supported by the Amsterdam UMC Corona Research Fund and the Talud Foundation (Stichting Talud). The current analyses were supported by the Novo Nordisk Foundation [NNF21OC0067528].

Cardiovascular Risk Estimation Based on Country-of-Birth- and Country-of-Residence-Specific Scores among Migrants in the Netherlands: The HELIUS Study.

BACKGROUND: Regional and country-specific cardiovascular risk algorithms have been developed to improve CVD risk prediction. But it is unclear whether migrants' country-of-residence or country-of-birth algorithms agree in stratifying the CVD risk of these populations. We evaluated the risk stratification by the different algorithms, by comparing migrant country-of-residence-specific scores to migrant country-of-birth-specific scores for ethnic minority populations in the Netherlands. METHOD: data from the HELIUS study was used in estimating the CVD risk scores for participants using five laboratory-based (Framingham, Globorisk, Pool Cohort Equation II, SCORE II, and WHO II) and three nonlaboratory-based (Framingham, Globorisk, and WHO II) risk scores with the risk chart for the Netherlands. For the Globorisk, WHO II, and SCORE II risk scores, we also computed the risk scores using risk charts specified for the migrant home country. Risk categorization was first done according to the specification of the risk algorithm and then simplified to low (green), moderate (yellow and orange), and high risk (red). RESULTS: we observed differences in risk categorization for different risk algorithms ranging from 0% (Globorisk) to 13% (Framingham) for the high-risk category, as well as differences in the country-of-residence- and country-of-birth-specific scores. Agreement between different scores ranged from none to moderate. We observed a moderate agreement between the Netherlands-specific SCORE II and the country-of-birth SCORE II for the Turkish and a nonagreement for the Dutch Moroccan population. CONCLUSION: disparities exist in the use of the country-of-residence-specific, as compared to the country-of-birth, risk algorithms among ethnic minorities living in the Netherlands. Hence, there is a need for further validation of country-of-residence- and country-of-birth-adjusted scores to ascertain appropriateness and reliability.

Epigenome-wide association study of plasma lipids in West Africans: the RODAM study.

BACKGROUND: DNA-methylation has been associated with plasma lipid concentration in populations of diverse ethnic backgrounds, but epigenome-wide association studies (EWAS) in West-Africans are lacking. The aim of this study was to identify DNA-methylation loci associated with plasma lipids in Ghanaians. METHODS: We conducted an EWAS using Illumina 450k DNA-methylation array profiles of extracted DNA from 663 Ghanaian participants. Differentially methylated positions (DMPs) were examined for association with plasma total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, and triglycerides concentrations using linear regression models adjusted for age, sex, body mass index, diabetes mellitus, and technical covariates. Findings were replicated in independent cohorts of different ethnicities. FINDINGS: We identified one significantly associated DMP with triglycerides (cg19693031 annotated to TXNIP, regression coefficient beta -0.26, false discovery rate adjusted p-value 0.001), which replicated in-silico in South African Batswana, African American, and European populations. From the top five DMPs with the lowest nominal p-values, two additional DMPs for triglycerides (CPT1A, ABCG1), two DMPs for LDL-cholesterol (EPSTI1, cg13781819), and one for TC (TXNIP) replicated. With the exception of EPSTI1, these loci are involved in lipid transport/metabolism or are known GWAS-associated loci. The top 5 DMPs per lipid trait explained 9.5% in the variance of TC, 8.3% in LDL-cholesterol, 6.1% in HDL-cholesterol, and 11.0% in triglycerides. INTERPRETATION: The top DMPs identified in this study are in loci that play a role in lipid metabolism across populations, including West-Africans. Future studies including larger sample size, longitudinal study design and translational research is needed to increase our understanding on the epigenetic regulation of lipid metabolism among West-African populations. FUNDING: European Commission under the Framework Programme (grant number: 278901).

Associations of psychosocial stress with type 2 diabetes and glycaemic control among Ghanaians: The RODAM study.

BACKGROUND: The extent to which psychosocial stress relates to type 2 diabetes among sub-Saharan Africans is not well understood. We assessed associations of psychosocial stresses with type 2 diabetes status and glycaemic control among Ghanaians. METHODS: We used data from Research on Obesity and Diabetes among African Migrants (RODAM) study. We performed logistic and linear regression models to assess association of psychosocial stresses with type 2 diabetes and HbA1c respectively with adjustments for age, sex, education and other stresses. We also assessed moderation effects of migration status (migrant Ghanaians vs. non-migrant Ghanaians), age, sex and education by adding interaction terms in models. RESULTS: Four thousand eight hundred and forty one Ghanaians were included with 44% resident in Ghana, 62% women, mean age of 46 years and 10% having type 2 diabetes. Psychosocial stress at home and at work were not associated with type 2 diabetes or HbA1c levels. Negative life events in past 12 months were negatively associated with type 2 diabetes (adjusted odds ratio = 0.93, 95% CI 0.87-0.99). Perceived discrimination was positively associated with type 2 diabetes (aOR = 1.01, 95% CI 1.004-1.03). Both associations were more pronounced in men. Perceived discrimination was also positively associated with HbA1c levels, especially among those with type 2 diabetes (adjusted ß = 0.01, 95% CI 0.007-0.02). CONCLUSIONS: Perceived discrimination and negative life events are associated with type 2 diabetes and glycaemic control among Ghanaians, especially in men. Further studies are needed to identify context-specific mechanisms underlying these associations.

An explorative epigenome-wide association study of plasma renin and aldosterone concentration in a Ghanaian population: the RODAM study.

BACKGROUND: The epigenetic regulation of the renin-angiotensin-aldosterone system (RAAS) potentially plays a role in the pathophysiology underlying the high burden of hypertension in sub-Saharan Africans (SSA). Here we report the first epigenome-wide association study (EWAS) of plasma renin and aldosterone concentrations and the aldosterone-to-renin ratio (ARR). METHODS: Epigenome-wide DNA methylation was measured using the Illumina 450K array on whole blood samples of 68 Ghanaians. Differentially methylated positions (DMPs) were assessed for plasma renin concentration, aldosterone, and ARR using linear regression models adjusted for age, sex, body mass index, diabetes mellitus, hypertension, and technical covariates. Additionally, we extracted methylation loci previously associated with hypertension, kidney function, or that were annotated to RAAS-related genes and associated these with renin and aldosterone concentration. RESULTS: We identified one DMP for renin, ten DMPs for aldosterone, and one DMP associated with ARR. Top DMPs were annotated to the PTPRN2, SKIL, and KCNT1 genes, which have been reported in relation to cardiometabolic risk factors, atherosclerosis, and sodium-potassium handling. Moreover, EWAS loci previously associated with hypertension, kidney function, or RAAS-related genes were also associated with renin, aldosterone, and ARR. CONCLUSION: In this first EWAS on RAAS hormones, we identified DMPs associated with renin, aldosterone, and ARR in a SSA population. These findings are a first step in understanding the role of DNA methylation in regulation of the RAAS in general and in a SSA population specifically. Replication and translational studies are needed to establish the role of these DMPs in the hypertension burden in SSA populations.

Inequalities in COVID-19 deaths by migration background during the first wave, interwave period and second wave of the COVID-19 pandemic: a closed cohort study of 17 million inhabitants of the Netherlands.

BACKGROUND: It is not known how differences in COVID-19 deaths by migration background in the Netherlands evolved throughout the pandemic, especially after introduction of COVID-19 prevention measures targeted at populations with a migration background (in the second wave). We investigated associations between migration background and COVID-19 deaths across first wave of the pandemic, interwave period and second wave in the Netherlands. METHODS: We obtained multiple registry data from Statistics Netherlands spanning from 1 March 2020 to 14 March 2021 comprising 17.4 million inhabitants. We estimated incidence rate ratios for COVID-19 deaths by migration background using Poisson regression models and adjusted for relevant sociodemographic factors. RESULTS: Populations with a migration background, especially those with Turkish, Moroccan and Surinamese background, exhibited higher risk of COVID-19 deaths than the Dutch origin population throughout the study periods. The elevated risk of COVID-19 deaths among populations with a migration background (as compared with Dutch origin population) was around 30% higher in the second wave than in the first wave. CONCLUSIONS: Differences in COVID-19 deaths by migration background persisted in the second wave despite introduction of COVID-19 prevention measures targeted at populations with a migration background in the second wave. Research on explanatory mechanisms and novel prevention measures are needed to address the ongoing differences in COVID-19 deaths by migration background.

An epigenome-wide association study of insulin resistance in African Americans.

BACKGROUND: African Americans have a high risk for type 2 diabetes (T2D) and insulin resistance. Studies among other population groups have identified DNA methylation loci associated with insulin resistance, but data in African Americans are lacking. Using DNA methylation profiles of blood samples obtained from the Illumina Infinium® HumanMethylation450 BeadChip, we performed an epigenome-wide association study to identify DNA methylation loci associated with insulin resistance among 136 non-diabetic, unrelated African American men (mean age 41.6 years) from the Howard University Family Study. RESULTS: We identified three differentially methylated positions (DMPs) for homeostatic model assessment of insulin resistance (HOMA-IR) at 5% FDR. One DMP (cg14013695, HOXA5) is a known locus among Mexican Americans, while the other two DMPs are novel-cg00456326 (OSR1; beta = 0.027) and cg20259981 (ST18; beta = 0.010). Although the cg00456326 DMP is novel, the OSR1 gene has previously been found associated with both insulin resistance and T2D in Europeans. The genes HOXA5 and ST18 have been implicated in biological processes relevant to insulin resistance. Differential methylation at the significant HOXA5 and OSR1 DMPs is associated with differences in gene expression in the iMETHYL database. Analysis of differentially methylated regions (DMRs) did not identify any epigenome-wide DMRs for HOMA-IR. We tested transferability of HOMA-IR associated DMPs from five previous EWAS in Mexican Americans, Indian Asians, Europeans, and European ancestry Americans. Out of the 730 previously reported HOMA-IR DMPs, 47 (6.4%) were associated with HOMA-IR in this cohort of African Americans. CONCLUSIONS: The findings from our study suggest substantial differences in DNA methylation patterns associated with insulin resistance across populations. Two of the DMPs we identified in African Americans have not been reported in other populations, and we found low transferability of HOMA-IR DMPs reported in other populations in African Americans. More work in African-ancestry populations is needed to confirm our findings as well as functional analyses to understand how such DNA methylation alterations contribute to T2D pathology.

COVID-19 Impacts Across Multiple Life Domains of Vulnerable Socio-Demographic Groups Including Migrants: A Descriptive Cross-Sectional Study.

Objectives: We assessed the impacts of COVID-19 on multiple life domains across socio-demographic groups in Netherlands. Methods: After the first COVID-19 wave, we distributed online questionnaires among 13,031 participants of the multi-ethnic HELIUS cohort. Questionnaires contained questions on changes in income status, healthy behaviors, mental health, and access to non-COVID-19 health care. We then calculated differences in adjusted proportions of participants that reported negative changes across multiple life domains by migration background, age, sex, education, and occupation. Results: 4,450 individuals (35%) responded, of which 4,294 were included. Older populations and men seemed to be less vulnerable to negative changes in multiple life domains during the COVID-19 pandemic as compared to the pre-pandemic period, while populations with a migration background and lower education/occupation groups seemed to be more vulnerable to negative changes. Conclusion: Not all populations vulnerable to SARS-CoV-2 infection and mortality are also more vulnerable to COVID-19 impacts across multiple other life domains. Targeted interventions are needed in socio-demographic groups that are most impacted by COVID-19 in various life domains to prevent a further increase of their already increased risk of chronic diseases after the pandemic.

The Magnitude and Directions of the Associations between Early Life Factors and Metabolic Syndrome Differ across Geographical Locations among Migrant and Non-Migrant Ghanaians-The RODAM Study.

BACKGROUND: Early-life factors (ELFs) such as childhood nutrition and childhood socio-economic status could be the drivers of the increase in metabolic syndrome (MetSyn) among African populations, but data are lacking. This study evaluated whether markers of childhood nutritional status and childhood socio-economic status were associated with MetSyn in adulthood among migrant Ghanaians living in Europe and non-migrant Ghanaians living in Ghana. METHODS: Data from the Research on Obesity and Diabetes among African Migrants (RODAM) study, involving 2008 migrants and 2320 non-migrants aged ≥25 years, were analysed for this study. We used leg-length to height ratio (LHR), which is an anthropometric marker of childhood nutritional status, and parental education, which is a marker of childhood socio-economic status, as proxies. Adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) were calculated by logistic regression with adjustments for demographic and lifestyle factors. RESULTS: Parental education was higher among Ghanaians in Europe than among residents in rural and urban Ghana. The prevalence of MetSyn was 18.5%, 27.7% and 33.5% for rural, urban, and migrant residents, respectively. LHR was inversely associated with MetSyn among migrants. Compared with high paternal education, individuals with low paternal education had lower odds of MetSyn in migrants (AOR 0.71 95% CI 0.54-0.94). In contrast, compared with high maternal education, individuals with intermediate maternal education had higher odds of MetSyn in urban Ghanaians (AOR 4.53 95% CI 1.50-3.74). No associations were found among rural Ghanaians. CONCLUSION: The magnitude and direction of the associations between ELFs and MetSyn differ across geographical locations. Intermediate maternal education was positively associated with MetSyn among urban Ghanaians, while LHR and low paternal education were inversely associated with MetSyn among migrant Ghanaians. Further research into the interplay of genetics, environment and behaviour is needed to elucidate the underlying pathological mechanisms of MetSyn amongst migrants.

Reduced Rank Regression-Derived Dietary Patterns Related to the Fatty Liver Index and Associations with Type 2 Diabetes Mellitus among Ghanaian Populations under Transition: The RODAM Study.

The Fatty Liver Index (FLI) is a proxy for the steatotic component of non-alcoholic fatty liver disease (NAFLD). For sub-Saharan African populations, the contribution of dietary factors to the development of NAFLD in the etiology of type 2 diabetes mellitus (T2DM) remains to be clarified. We identified sex-specific dietary patterns (DPs) related to the FLI using reduced ranked regression (RRR) and evaluated the associations of these DPs with T2DM. This analysis used data from the RODAM, a multi-center cross-sectional study of Ghanaian populations living in Ghana and Europe. The daily intake frequencies of 30 food groups served as the predictor variables, while the FLI was the response variable. The odds ratios and 95% confidence intervals for T2DM were calculated per one standard deviation increase in the DP score using logistic regression. In males, the DP score explained 9.9% of the variation in their food intake and 16.0% of the variation in the FLI. This DP was characterized by high intakes of poultry, whole-grain cereals, coffee and tea, condiments, and potatoes, and the chance of T2DM was 45% higher per 1 DP score-SD (Model 2). Our results indicate that the intake of modernized foods was associated with proxies of NAFLD, possibly underlying the metabolic pathways to developing T2DM.

Metabolic-associated Fatty Liver Disease as Assessed by the Fatty Liver Index Among Migrant and Non-migrant Ghanaian Populations.

BACKGROUND AND AIMS: Metabolic-associated fatty liver disease (MAFLD) is driven by high caloric intake and sedentary lifestyle. Migration towards high income countries may induce these driving factors; yet, the influence of such on the prevalence of MAFLD is clearly understudied. Here, we investigated the Fatty Liver Index (FLI), a proxy of steatosis in MAFLD, after migration of Ghanaian subjects. METHODS: Cross-sectional data of 5282 rural, urban and migrant participants from the Research on Obesity and Diabetes among African Migrants (also known as RODAM) study were analyzed with logistic regression for geographical differences in FLI and associations with type 2 diabetes mellitus (T2DM), waist-to-hip ratio, and 10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD). RESULTS: Both FLI and the proportion with an FLI indicative of MAFLD steatosis (FLI ≥60) were higher in migrants compared with non-migrants. Prevalence of elevated FLI (FLI ≥60) in non-migrant males was 4.2% compared to 28.9% in migrants. For females, a similar gradient was observed, from 13.6% to 36.6% respectively. Compared to rural residents, the odds for a FLI ≥60 were higher in migrants living in urban Europe (odds ratio [OR] 9.02, 95% confidence interval [CI]: 5.02-16.20 for men, and 4.00, 95% CI: 3.00-5.34 for women). Compared to controls, the ORs for FLI ≥60 were 2.43 (95% CI: 1.73-3.41) for male T2DM cases and 2.02 (95% CI: 1.52-2.69) for female T2DM cases. One-unit higher FLI was associated with an elevated (≥7.5%) 10-year ASCVD risk (OR: 1.051, 95% CI: 1.041-1.062 for men, and 1.020, 95% CI: 1.015-1.026 for women). CONCLUSIONS: FLI as a proxy for MAFLD increased stepwise in Ghanaians from rural areas, through urban areas, to Europe. Our results clearly warrant awareness for MAFLD in migrant population as well as confirmation with imaging modalities.

Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases.

Molecular mechanisms at the intersection of inflammation and cardiovascular diseases (CVD) among Africans are still unknown. We performed an epigenome-wide association study to identify loci associated with serum C-reactive protein (marker of inflammation) among Ghanaians and further assessed whether differentially methylated positions (DMPs) were linked to CVD in previous reports, or to estimated CVD risk in the same population. We used the Illumina Infinium® HumanMethylation450 BeadChip to obtain DNAm profiles of blood samples in 589 Ghanaians from the RODAM study (without acute infections, not taking anti-inflammatory medications, CRP levels < 40 mg/L). We then used linear models to identify DMPs associated with CRP concentrations. Post-hoc, we evaluated associations of identified DMPs with elevated CVD risk estimated via ASCVD risk score. We also performed subset analyses at CRP levels ≤10 mg/L and replication analyses on candidate probes. Finally, we assessed for biological relevance of our findings in public databases. We subsequently identified 14 novel DMPs associated with CRP. In post-hoc evaluations, we found that DMPs in PC, BTG4 and PADI1 showed trends of associations with estimated CVD risk, we identified a separate DMP in MORC2 that was associated with CRP levels ≤10 mg/L, and we successfully replicated 65 (24%) of previously reported DMPs. All DMPs with gene annotations (13) were biologically linked to inflammation or CVD traits. We have identified epigenetic loci that may play a role in the intersection between inflammation and CVD among Ghanaians. Further studies among other Africans are needed to confirm our findings.

DNA methylation as the link between migration and the major noncommunicable diseases: the RODAM study.

Aim: We assessed epigenome-wide DNA methylation (DNAm) differences between migrant and non-migrant Ghanaians. Materials & methods: We used the Illumina Infinium® HumanMethylation450 BeadChip to profile DNAm of 712 Ghanaians in whole blood. We used linear models to detect differentially methylated positions (DMPs) associated with migration. We performed multiple post hoc analyses to validate our findings. Results: We identified 13 DMPs associated with migration (delta-beta values: 0.2-4.5%). Seven DMPs in CPLX2, EIF4E3, MEF2D, TLX3, ST8SIA1, ANG and CHRM3 were independent of extrinsic genomic influences in public databases. Two DMPs in NLRC5 were associated with duration of stay in Europe among migrants. All DMPs were biologically linked to migration-related factors. Conclusion: Our findings provide the first insights into DNAm differences between migrants and non-migrants.