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.

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.

Association between Practising Religion and Cardiovascular Disease Risk among Ghanaian Non-Migrants and Migrants in Europe: The RODAM Study

(1) Background: Sub-Saharan African migrants residing in high-income countries are more affected by cardiovascular diseases (CVDs) and associated risk factors than host populations for unclear reasons. The aim was to explore the associations of religion and religious affiliations with CVD risk among Ghanaian non-migrants and migrants in Europe. (2) Methods: The 10-year CVD risk was estimated using pooled cohort equations for 3004 participants from the cross-sectional Research on Obesity and Diabetes among African Migrants (RODAM) study. Logistic regression analyses were conducted to assess associations between religion and elevated CVD risk (score ≥ 7.5) with adjustment for covariates. (3) Results: Religious men in Europe had a lower 10-year CVD risk compared with non-religious men (adjusted OR 0.51; 95% confidence interval 0.30–0.85), specifically men affiliated with Seventh-Day Adventism (0.24; 0.11–0.53) followed by other affiliations (0.32; 0.11–0.94) and Roman Catholicism (0.42; 0.21–0.86). The opposite was found in Ghana, with religious women having higher odds for elevated 10-year CVD risk (1.53; 1.02–2.30) compared with their non-religious counterparts, specifically women affiliated with Reformed Christianity (1.73; 1.03–2.90) and other denominations (2.81; 1.20–6.54). Associations were not significant for men in Ghana and women in Europe. Adjustments for social support, stress, and health behaviors did not meaningfully alter the associations. (4) Conclusions: Christian religious Ghanaian men living in Europe seem to have lower CVD risk compared with their non-religious counterparts, while Christian religious women in Ghana appear to have increased CVD risk. Further unravelling the contributing factors and the differences between sex and environmental settings is needed.

Association between C reactive protein and microvascular and macrovascular dysfunction in sub-Saharan Africans with and without diabetes: the RODAM study

IntroductionAlthough inflammation assessed by elevated C reactive protein (CRP) concentration is known to be associated with risk of cardiovascular disease, its association with microvascular and macrovascular dysfunction in diabetes and non-diabetes remains unclear. We examined the association between CRP and diabetes and associated microvascular and macrovascular dysfunction in sub-Saharan Africans with and without diabetes.Research design and methodsCross-sectional analyses of baseline data from the multicenter RODAM study (Research on Obesity and Diabetes among African Migrants) including 5248 Ghanaians (583 with diabetes, 4665 without diabetes) aged 25–70 years were done. Logistic regression analyses were used to examine the associations between CRP Z-scores and diabetes and microvascular (nephropathy) and macrovascular (peripheral artery disease (PAD)) dysfunction, with adjustments for age, sex, site of residence, smoking, body mass index, systolic blood pressure, and low-density lipoprotein cholesterol.ResultsIn the fully adjusted models, higher CRP concentration was significantly associated with diabetes (adjusted OR 1.13; 95% CI 1.05 to 1.21, p=0.002). In participants with diabetes, higher CRP concentration was associated with PAD (1.19; 1.03 to 1.41, p=0.046) but not nephropathy (1.13; 0.97 to 1.31, p=0.120). Among participants without diabetes, higher CRP concentration was associated with higher odds of PAD (1.10; 1.01 to 1.21, p=0.029) and nephropathy (1.12; 1.04 to 1.22, p=0.004).ConclusionsIn this study, higher CRP concentration was associated with higher odds of diabetes in sub-Saharan Africans. Also, higher CRP concentration was associated with higher odds of nephropathy and PAD in non-diabetes and higher odds of PAD in diabetes. CRP may be an important marker for assessment of risk of diabetes and risk for PAD and nephropathy in sub-Saharan Africans with and without diabetes.