Batterham, M. | bioRxiv Science

bioRxiv2019

The current obesity “epidemic”: segregation of familial genetic risk in NHANES cohort supports a major role for large genetic effects

The continuing increase in many countries in adult body mass index (BMI kg/m2) and its dispersion is contributed to by interaction between genetic susceptibilities and an increasingly obesogenic environment (OE). The determinants of OE-susceptibility are unresolved, due to uncertainty around relevant genetic and environmental architecture. We aimed to test the multi-modal distributional predictions of a Mendelian genetic architecture based on collectively common, but individually rare, large-effect variants and their ability to account for current trends in a large population-based sample. We studied publicly available adult BMI data (n = 9102) from 3 cycles of NHANES (1999, 2005, 2013). A first degree family history of diabetes served as a binary marker (FH0/FH1) of genetic obesity susceptibility. We tested for multi-modal BMI distributions non-parametrically using kernel-smoothing and conditional quantile regression (CQR), obtained parametric fits to a Mendelian model in FH1, and estimated FH x OE interactions in CQR models and ANCOVA models incorporating secular time. Non-parametric distributional analyses were consistent with multi-modality and fits to a Mendelian model in FH1 reliably identified 3 modes. Mode separation accounted for ~40% of BMI variance in FH1 providing a lower bound for the contribution of large effects. CQR identified strong FH x OE interactions and FH1 accounted for ~60% of the secular trends in BMI and its SD in ANCOVA models. Multimodality in the FH effect is inconsistent with a predominantly polygenic, small effect architecture and we conclude that large genetic effects interacting with OE provide a better quantitative explanation for current trends in BMI.

genetics↗

bioRxiv2019

Vitamin D deficiency during pregnancy and its associated factors among third trimester Malaysian pregnant women

BackgroundDespite perennial sunshine, vitamin D deficiency is prevalent among Malaysian especially pregnant women.\n\nObjectiveTo determine the vitamin D status and its associated factors among third trimester pregnant women attending government health clinics in Selangor and Kuala Lumpur, Malaysia.\n\nMethodsInformation on socio-demographic characteristics, obstetrical history, vitamin D intake, supplement use, and sun exposure were obtained through face-to-face interviews. Serum 25-hydroxyvitamin D concentration was measured and classified as deficient (< 30 nmol/L), insufficient (30-50 nmol/L), and sufficient ([≥] 50 nmol/L).\n\nResultsOf the 535 pregnant women recruited, 42.6% were vitamin D deficient. They consumed an average of 8.7 {+/-} 6.7 g of vitamin D daily. A total of 80.4% of the vitamin D were obtained from the food sources, while 19.6% were from dietary supplements. Fish and fish products showed the highest contribution to vitamin D intake (35.8%). The multivariate generalized linear mixed models, with clinic as a random effect, indicates that higher intake of vitamin D is associated with lower risk of vitamin D deficiency among pregnant women (OR = 0.96; 95% CI = 0.93-0.99). Non-Malay pregnant women had lower odds of having vitamin D deficiency (OR = 0.13; 95% CI = 0.04-0.37) compared to Malays. No associations were found between age, educational level, monthly household income, work status, gravidity, parity, pre-pregnancy body mass index, total hours of sun exposure, total percentage of body surface area, and sun exposure index per day with vitamin D deficiency.\n\nConclusionsVitamin D deficiency is prevalent among Malaysian pregnant women. Considering the possible adverse obstetric and fetal outcomes of vitamin D deficiency during pregnancy, antenatal screening of vitamin D levels and nutrition education should be emphasised by taking into consideration ethnic differences.

epidemiology↗