Publications

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10−9 at rs8018720 in SEC23A, and P = 1.9×10−14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene–gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

Bariatric (or metabolic) surgery is the most effective treatment for severe obesity, resulting in sustained weight loss and rapid improvement in metabolic outcomes. However, it is currently unknown what molecular changes are induced by the surgery, how they relate to the health improvements, how early they occur, and whether they are maintained over time. In this study, we characterized early gene expression changes following surgery in blood samples from the "Personalised Medicine for Morbid Obesity" cohort. We observed widespread changes in gene expression only a few days after surgery. Pathways related to immune response were affected, in particular with a decreased expression of the NF-κB pathway and neutrophil cytotoxic activity genes, suggesting a reduction of the inflammatory state typically associated with obesity. Metabolic signaling was also affected, with decreased expression of genes from pathways related to glucagon and insulin secretion, and key regulators such as the appetite-controlling hormone ghrelin. Comparisons to publicly available transcriptomics datasets showed that beyond these specific changes, bariatric surgery induces a transcriptome-wide reversal of expression changes associated with obesity and with forms of type 2 diabetes related to obesity. Comparisons to transcriptomics studies with longer-term follow-ups after bariatric surgery showed that a large fraction of early-induced expression changes likely persist for several months. Taken together, we show that previously unreported early changes in blood gene expression after bariatric surgery provide in-depth insights into the resolution of the chronic inflammation associated with severe obesity and its connection with metabolic improvement.

Importance: The Mediterranean diet, and other dietary patterns rich in fruits and vegetables, have been linked to lower risk of frailty in older adults. However, not all plant-based diets are necessarily healthful, and no previous study has evaluated the role of the quality of plant-based dietary patterns in frailty risk. Objective: To assess the association between plant-based diet quality and risk of frailty. Design, setting, and participants: Prospective cohort with 82,234 women aged ≥60y from the Nurses’ Health Study, who were followed from 1990 through 2014. The dates of analysis were April 14 to -June 23, 2021. Exposures: Dietary data were collected every 4-y using a validated semi-quantitative food frequency questionnaire. The plant-based diet quality was assessed with 2 indices (range 18 - 90 points).: a) Healthful Plant-Based Diet Index (hPDI), where healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, tea/coffee) received positive scores, while less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, sweets/desserts) and animal foods received reverse scores; and b) Unhealthful Plant-Based Diet Index (uPDI) where positive scores were given to less healthy plant foods and reverse scores to healthy plant foods and animal foods. Main outcomes: Frailty incidence was assessed every 4 years, being defined as having ≥3 of the following 5 criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥5 illnesses, and weight loss ≥5%. Methods: Multivariable-adjusted Cox proportional-hazards models were used to estimate hazard ratios (HRs), and their 95% confidence interval (CI). Results: We identified 12,910 incident cases of frailty over 1,176,401 person-year follow-up. In the multivariable analysis, the hPDI was inversely associated with the risk of frailty (HR for the highest vs. lowest quintile: 0.69, 95% CI: 0.65-0.73; p-trend<0.001). In addition, a 10-unit increment in the hPDI was associated with a relative 20% lower risk of frailty. Conversely, a direct association was found between the uPDI and risk of frailty (HR highest vs. lowest quintile: 1.41, 95% CI: 1.32-1.49]; p-trend<0.001). These associations were consistent for each frailty criterion, among participants with no frailty criteria at baseline, after excluding participants with diabetes, cancer, and CVD at baseline, for alternative versions of the PDIs, in subgroup analysis by categories of potential confounders, and in latency analysis. Conclusions and relevance: A healthful plant-based diet was associated with lower risk of frailty whereas an unhealthful plant-based diet was associated with higher risk.

OBJECTIVES: Several plant-based foods have been associated with a lower risk of Crohn's disease (CD) and ulcerative colitis (UC), but not all plant-based foods are healthy. We aimed to examine the association of various plant-based diets with the risk of CD and UC. METHODS: We followed 169 945 women in the Nurses’ Health Study and Nurses’ Health Study II for up to 32 years. Plant-based diets were assessed by three indices derived from the food frequency questionnaires: an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI), and an unhealthful plant-based diet index (uPDI). Self-reported CD and UC were confirmed through medical record review. RESULTS: We documented 320 incident CD cases and 404 incident UC cases during 4 317 561 person-years. A higher hPDI was associated with a lower risk of UC (hazard ratio [HR] comparing extreme quintiles: 0.67; 95% confidence interval [CI]: 0.47–0.94; P-trend = 0.02). In contrast, the uPDI was associated with an increased risk of CD (HR: 1.67; 95% CI: 1.11–2.51; P-trend = 0.002) and UC (HR: 1.65; 95% CI: 1.15–2.35; P-trend = 0.03). Replacing refined grains, sugar-sweetened beverages, and sweets/desserts with an equal serving of fruits or vegetables was associated with lower risk of CD and UC. CONCLUSIONS: A healthful plant-based diet rich in fruits and vegetables was associated with a lower UC risk, whereas a plant-based diet emphasizing less healthy plant foods such as refined grains, sugar-sweetened beverages, and sweets/desserts was associated with a higher CD and UC risk. FUNDING SOURCES: National Institutes of Health.

This paper describes the fabrication and the performance of microfluidic paper-based electrochemical sensing devices (we call the microfluidic paper-based electrochemical devices, µPEDs). The µPEDs comprise paper-based microfluidic channels patterned by photolithography or wax printing, and electrodes screen-printed from conducting inks (e.g., carbon or Ag/AgCl). We demonstrated that the µPEDs are capable of quantifying the concentrations of various analytes (e.g., heavy-metal ions and glucose) in aqueous solutions. This low-cost analytical device should be useful for applications in public health, environmental monitoring, and the developing world.

OBJECTIVE The associations of prenatal exposures to maternal prepregnancy overweight and gestational diabetes mellitus (GDM) with offspring overweight are controversial. Research estimating risk for offspring overweight due to these exposures, separately and concomitantly, is limited. RESEARCH DESIGN AND METHODS Prevalence of overweight and abdominal obesity at age 16 years and odds ratios (ORs) for prenatal exposures to maternal prepregnancy overweight and GDM were estimated in participants of the prospective longitudinal Northern Finland Birth Cohort of 1986 ( N = 4,168). RESULTS The prevalence and estimates of risk for overweight and abdominal obesity were highest in those exposed to both maternal prepregnancy overweight and GDM (overweight prevalence 40% [OR 4.05], abdominal obesity prevalence 25.7% [3.82]). Even in offspring of mothers with a normal oral glucose tolerance test during pregnancy, maternal prepregnancy overweight is associated with increased risk for these outcomes (overweight prevalence 27.9% [2.56], abdominal obesity prevalence 19.5% [2.60]). In offspring of women with prepregnancy normal weight, the prevalence or risks of the outcomes were not increased by prenatal exposure to GDM. These estimates of risk were adjusted for parental prepregnancy smoking, paternal overweight, and offspring sex and size at birth. CONCLUSIONS Maternal prepregnancy overweight is an independent risk factor for offspring overweight and abdominal obesity at age 16 years. The risks are highest in offspring with concomitant prenatal exposure to maternal prepregnancy overweight and GDM, whereas the risks associated with GDM are only small.