Genome-Wide Association Analysis of Over 170,000 Individuals from the UK Biobank Identifies Seven Loci Associated with Dietary Approaches to Stop Hypertension (DASH) Diet.

Diet is a modifiable risk factor for common chronic diseases and mental health disorders, and its effects are under partial genetic control. To estimate the impact of diet on individual health, most epidemiological and genetic studies have focused on individual aspects of dietary intake. However, analysing individual food groups in isolation does not capture the complexity of the whole diet pattern. Dietary indices enable a holistic estimation of diet and account for the intercorrelations between food and nutrients. In this study we performed the first ever genome-wide association study (GWA) including 173,701 individuals from the UK Biobank to identify genetic variants associated with the Dietary Approaches to Stop Hypertension (DASH) diet. DASH was calculated using the 24 h-recall questionnaire collected by UK Biobank. The GWA was performed using a linear mixed model implemented in BOLT-LMM. We identified seven independent single-nucleotide polymorphisms (SNPs) associated with DASH. Significant genetic correlations were observed between DASH and several educational traits with a significant enrichment for genes involved in the AMP-dependent protein kinase (AMPK) activation that controls the appetite by regulating the signalling in the hypothalamus. The colocalization analysis implicates genes involved in body mass index (BMI)/obesity and neuroticism (ARPP21, RP11-62H7.2, MFHAS1, RHEBL1). The Mendelian randomisation analysis suggested that increased DASH score, which reflect a healthy diet style, is causal of lower glucose, and insulin levels. These findings further our knowledge of the pathways underlying the relationship between diet and health outcomes. They may have significant implications for global public health and provide future dietary recommendations for the prevention of common chronic diseases.

Genetic and Dietary Factors Influencing the Progression of Nuclear Cataract.

PURPOSE: To determine the heritability of nuclear cataract progression and to explore prospectively the effect of dietary micronutrients on the progression of nuclear cataract. DESIGN: Prospective cohort study. PARTICIPANTS: Cross-sectional nuclear cataract and dietary measurements were available for 2054 white female twins from the TwinsUK cohort. Follow-up cataract measurements were available for 324 of the twins (151 monozygotic and 173 dizygotic twins). METHODS: Nuclear cataract was measured using a quantitative measure of nuclear density obtained from digital Scheimpflug images. Dietary data were available from EPIC food frequency questionnaires. Heritability was modeled using maximum likelihood structural equation twin modeling. Association between nuclear cataract change and micronutrients was investigated using linear and multinomial regression analysis. The mean interval between baseline and follow-up examination was 9.4 years. MAIN OUTCOME MEASURES: Nuclear cataract progression. RESULTS: The best-fitting model estimated that the heritability of nuclear cataract progression was 35% (95% confidence interval [CI], 13-54), and individual environmental factors explained the remaining 65% (95% CI, 46-87) of variance. Dietary vitamin C was protective against both nuclear cataract at baseline and nuclear cataract progression (ß = -0.0002, P = 0.01 and ß = -0.001, P = 0.03, respectively), whereas manganese and intake of micronutrient supplements were protective against nuclear cataract at baseline only (ß = -0.009, P = 0.03 and ß = -0.03, P = 0.01, respectively). CONCLUSIONS: Genetic factors explained 35% of the variation in progression of nuclear cataract over a 10-year period. Environmental factors accounted for the remaining variance, and in particular, dietary vitamin C protected against cataract progression assessed approximately 10 years after baseline.

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process.

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.

Optic disc planimetry, corneal hysteresis, central corneal thickness, and intraocular pressure as risk factors for glaucoma.

PURPOSE: To determine whether corneal hysteresis and central corneal thickness are independent risk factors for glaucoma. DESIGN: A cross-sectional population-based cohort study. METHODS: Associations were tested between corneal hysteresis, measured in 1754 population-based subjects from the TwinsUK cohort, and glaucoma-related endophenotypes, including intraocular pressure (IOP), vertical cup-to-disc ratio, optic disc area, and optic disc cup area. Corneal hysteresis, IOP, and central corneal thickness (CCT) were measured; optic disc photographs were analyzed; and multivariable linear regression analysis was performed. RESULTS: Data were available on 1645 individuals. Multiple regression analysis showed corneal hysteresis to be significantly negatively associated with age (beta coefficient = -0.03, P < .00005) and IOP (beta coefficient = -0.06, P < .00005). Corneal hysteresis was also found to be associated with CCT (beta coefficient = 0.02, P < .0005). There was no significant association between corneal hysteresis and optic disc area (P = .6), cup area (P = .77), vertical cup-to-disc ratio (P = .51), or spherical equivalent (P = .08). CCT was also found to be significantly associated with IOP (beta coefficient = 3.3, P < .0005) and corneal hysteresis (beta coefficient = 9.4, P < .0005), but not with age (P = .59) or spherical equivalent (P = .16). CONCLUSION: In this large cohort of healthy British twins, we found no relationship between corneal hysteresis or CCT and quantitative measures of optic disc cupping, suggesting that corneal hysteresis and CCT are not independent risk factors for glaucoma.

Candidate gene study of macular response to supplemental lutein and zeaxanthin.

Supplementation with carotenoids is proposed to protect against age-related macular degeneration. There is, however, considerable variability in retinal macular pigment response, which may be due to underlying genetic variation. The purpose of this study was to determine whether genetic factors, which have been previously associated with cross-sectional macular pigment levels in the retina or serum lutein, also influence response to supplementation. To this end we conducted an association study in 310 subjects from the TwinsUK cohort between variants in 8 candidate genes and serum lutein and retinal macular pigment optical density (MPOD) levels before and after supplementation. Four variants were associated with MPOD response to supplementation (p < 0.05): rs11057841 (SCARB1), rs4926339 (RPE65), rs1929841 (ABCA1) and rs174534 (FADS1). We also confirmed previous associations between rs6564851 near BMCO1 (p < 0.001) and rs11057841 within SCARB1 (p = 0.01) and baseline measures of serum lutein; while the latter was also associated with MPOD response, none of the BMCO1 variants were. Finally, there was evidence for association between variants near RPE65 and ELOVL2 and changes in lutein concentration after supplementation. This study is the first to show association between genetic variants and response to carotenoids supplementation. Our findings suggest an important link between MP response and the biological processes of carotenoids transport and fatty acid metabolism.