[show abstract][hide abstract] ABSTRACT: To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
[show abstract][hide abstract] ABSTRACT: Black compared with non-Hispanic white Americans have higher systolic and diastolic blood pressure and rates of prehypertension/hypertension. Reasons for these adverse findings remain obscure. Analyses here focused on relations of foods/nutrients/urinary metabolites and higher black blood pressure for 369 black compared with 1190 non-Hispanic white Americans aged 40 to 59 years from 8 population samples. Multiple linear regression, standardized data from four 24-hour dietary recalls per person, two 24-hour urine collections, and 8 blood pressure measurements were used to quantitate the role of foods, nutrients, and metabolites in higher black blood pressure. Compared with non-Hispanic white Americans, blacks' average systolic/diastolic pressure was higher by 4.7/3.4 mm Hg (men) and 9.0/4.8 mm Hg (women). Control for higher body mass index of black women reduced excess black systolic/diastolic pressure to 6.8/3.8 mm Hg. Lesser intake of vegetables, fruits, grains, vegetable protein, glutamic acid, starch, fiber, minerals, and potassium, and higher intake of processed meats, pork, eggs, and sugar-sweetened beverages, along with higher cholesterol and higher Na/K ratio, related to in higher black blood pressure. Control for 11 nutrient and 10 non-nutrient correlates reduced higher black systolic/diastolic pressure to 2.3/2.3 mm Hg (52% and 33% reduction in men) and to 5.3/2.8 mm Hg (21% and 27% reduction in women). Control for foods/urinary metabolites had little further influence on higher black blood pressure. Less favorable multiple nutrient intake by blacks than non-Hispanic white Americans accounted, at least in part, for higher black blood pressure. Improved dietary patterns can contribute to prevention/control of more adverse black blood pressure levels.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Available data have indicated independent direct relations of dietary animal protein and meat to the blood pressure (BP) of individuals. OBJECTIVE: In this study, we aimed to assess whether BP is associated with the intake of dietary amino acids higher relatively in animal than in vegetable protein (alanine, arginine, aspartic acid, glycine, histidine, lysine, methionine, and threonine). DESIGN: The study was a cross-sectional epidemiologic study that involved 4680 persons aged 40-59 y from 17 random population samples in the People's Republic of China, Japan, the United Kingdom, and the United States. BP was measured 8 times at 4 visits; dietary data (83 nutrients and 18 amino acids) were from four 24-h dietary recalls and two 24-h urine collections. RESULTS: Dietary glycine and alanine (the percentage of total protein intake) were considered singly related directly to BP; with these 2 amino acids together in regression models (from model 1, which was controlled for age, sex, and sample, to model 5, which was controlled for 16 possible confounders), glycine, but not alanine, was significantly related to BP. Estimated average BP differences associated with a 2-SD higher glycine intake (0.71 g/24 h) were 2.0-3.0-mm Hg systolic BP (z = 2.97-4.32) stronger in Western than in East Asian participants. In Westerners, meat was the main dietary source of glycine but not in East Asians (Chinese: grains/flour and rice/noodles; Japanese: fish/shellfish and rice/noodles). CONCLUSION: Dietary glycine may have an independent adverse effect on BP, which possibly contributes to direct relations of animal protein and meat to BP.
American Journal of Clinical Nutrition 05/2013; · 6.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Epidemiologic evidence suggests that fruit consumption may lower the risk of cardiovascular diseases through blood pressure (BP)-lowering effects; little is known on the independent effect of raw fruit and fruit juice on BP. OBJECTIVE: The objective was to quantify associations of raw fruit and fruit juice consumption with BP by using cross-sectional data from the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP) of 4680 men and women aged 40-59 y from Japan, China, the United Kingdom, and the United States. DESIGN: During 4 visits, 8 BP, four 24-h dietary recalls, and two 24-h urine samples were collected. Country-specific multivariate-controlled linear regression coefficients, including adjustment for urinary sodium excretion, were estimated and pooled weighted by inverse of their variance. RESULTS: The average total raw fruit consumption varied from a mean ± SD 52 ± 65 g/1000 kcal in the United States to 68 ± 70 g/1000 kcal in China. Individual raw fruit intake was not associated with BP in pooled analyses for all countries or in participants from Western countries, although a positive association with diastolic BP was observed in East Asian participants (per 50 g/1000 kcal; 0.37 mm Hg; 95% CI: 0.02, 0.71). Positive relationships with diastolic BP were found for citrus fruit intake in Western consumers (per 25 g/1000 kcal; 0.47 mm Hg; 95% CI: 0.12, 0.81) and for apple intake in East Asian consumers (0.40 mm Hg; 95% CI: 0.03, 0.78). Among East Asian banana consumers, banana intake was inversely associated with diastolic BP (-1.01 mm Hg; 95% CI: -1.88, -0.02). Fruit juice intake, which was negligible in Asia, was not related to BP in Western countries. CONCLUSION: Consistent associations were not found between raw fruit and fruit juice consumption of individuals and BP. This observational study was registered at www.clinicaltrials.gov as NCT00005271.
American Journal of Clinical Nutrition 04/2013; · 6.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: Obesity often clusters with other major cardiovascular disease risk factors, yet a subset of the obese appears to be protected from these risks. Two obesity phenotypes are described, (i) "metabolically healthy" obese, broadly defined as body mass index (BMI) ≥ 30 kg/m(2) and favorable levels of blood pressure, lipids, and glucose; and (ii) "at risk" obese, BMI ≥ 30 with unfavorable levels of these risk factors. More than 30% of obese American adults are metabolically healthy. Diet and activity determinants of obesity phenotypes are unclear. We hypothesized that metabolically healthy obese have more favorable behavioral factors, including less adverse diet composition and higher activity levels than at risk obese in the multi-ethnic group of 775 obese American adults ages 40-59 years from the International Population Study on Macro/Micronutrients and Blood Pressure (INTERMAP) cohort. DESIGN AND METHODS: In gender-stratified analyses, mean values for diet composition and activity behavior variables, adjusted for age, race, and education, were compared between metabolically healthy and at risk obese. RESULTS: Nearly one in five (149/775 or 19%) of obese American INTERMAP participants were classified as metabolically healthy obese. Diet composition and most activity behaviors were similar between obesity phenotypes, although metabolically healthy obese women reported higher sleep duration than at risk obese women. CONCLUSIONS: These results do not support hypotheses that diet composition and/or physical activity account for the absence of cardiometabolic abnormalities in metabolically healthy obese.
[show abstract][hide abstract] ABSTRACT: BACKGROUND:: Extremely low-frequency magnetic fields are designated as possibly carcinogenic in humans, based on an epidemiologic association with childhood leukemia. Evidence for associations with adult cancers is weaker and inconsistent. METHODS:: We conducted a case-control study to investigate risks of adult cancers in relation to distance and extremely low-frequency magnetic fields from high-voltage overhead power lines using National Cancer Registry Data in England and Wales, 1974-2008. The study included 7823 leukemia, 6781 brain/central nervous system cancers, 9153 malignant melanoma, 29,202 female breast cancer cases, and 79,507 controls frequency-matched on year and region (three controls per case except for female breast cancer, one control per case) 15-74 years of age living within 1000 m of a high-voltage overhead power line. RESULTS:: There were no clear patterns of excess risk with distance from power lines. After adjustment for confounders (age, sex [except breast cancer], deprivation, rurality), for distances closest to the power lines (0-49 m) compared with distances 600-1000 m, odds ratios (ORs) ranged from 0.82 (95% confidence interval = 0.61-1.11; 66 cases) for malignant melanoma to 1.22 (0.88-1.69) for brain/central nervous system cancer. We observed no meaningful excess risks and no trends of risk with magnetic field strength for the four cancers examined. In adjusted analyses at the highest estimated field strength, ≥1000 nanotesla (nT), compared with <100 nT, ORs ranged from 0.68 (0.39-1.17) for malignant melanoma to 1.08 (0.77-1.51) for female breast cancer. CONCLUSION:: Our results do not support an epidemiologic association of adult cancers with residential magnetic fields in proximity to highvoltage overhead power lines.
[show abstract][hide abstract] ABSTRACT: In this study, Prokopenko and colleagues provide novel evidence for causal relationship between adiposity and heart failure and increased liver enzymes using a Mendelian randomization study design.
Please see later in the article for the Editors' Summary
[show abstract][hide abstract] ABSTRACT: Background. Research to date on health effects associated with incineration has found limited evidence of health risks, but many previous studies have been constrained by poor exposure assessment. This paper provides a comparative assessment of atmospheric dispersion modelling and distance from source (a commonly used proxy for exposure) as exposure assessment methods for pollutants released from incinerators. Methods. Distance from source and the atmospheric dispersion model ADMS-Urban were used to characterise ambient exposures to particulates from two municipal solid waste incinerators (MSWIs) in the UK. Additionally an exploration of the sensitivity of the dispersion model simulations to input parameters was performed. Results. The model output indicated extremely low ground level concentrations of PM10, with maximum concentrations of <0.01 μ g/m(3). Proximity and modelled PM10 concentrations for both MSWIs at postcode level were highly correlated when using continuous measures (Spearman correlation coefficients ~ 0.7) but showed poor agreement for categorical measures (deciles or quintiles, Cohen's kappa coefficients ≤ 0.5). Conclusion. To provide the most appropriate estimate of ambient exposure from MSWIs, it is essential that incinerator characteristics, magnitude of emissions, and surrounding meteorological and topographical conditions are considered. Reducing exposure misclassification is particularly important in environmental epidemiology to aid detection of low-level risks.
Journal of Environmental and Public Health 01/2013; 2013:560342.
[show abstract][hide abstract] ABSTRACT: Gene-environment interaction studies offer the prospect of robust causal inference through both gene identification and instrumental variable approaches. As such they are a major and much needed development. However, conducting these studies using traditional methods, which require direct participant contact, is resource intensive. The ability to conduct gene-environment interaction studies remotely would reduce costs and increase capacity.
To develop a platform for the remote conduct of gene-environment interaction studies.
A random sample of 15,000 men and women aged 50+ years and living in Cardiff, South Wales, of whom 6,012 were estimated to have internet connectivity, were mailed inviting them to visit a web-site to join a study of successful ageing. Online consent was obtained for questionnaire completion, cognitive testing, re-contact, record linkage and genotyping. Cognitive testing was conducted using the Cardiff Cognitive Battery. Bio-sampling was randomised to blood spot, buccal cell or no request.
A heterogeneous sample of 663 (4.5% of mailed sample and 11% of internet connected sample) men and women (47% female) aged 50-87 years (median = 61 yrs) from diverse backgrounds (representing the full range of deprivation scores) was recruited. Bio-samples were donated by 70% of those agreeing to do so. Self report questionnaires and cognitive tests showed comparable distributions to those collected using face-to-face methods. Record linkage was achieved for 99.9% of participants.
This study has demonstrated that remote methods are suitable for the conduct of gene-environment interaction studies. Up-scaling these methods provides the opportunity to increase capacity for large-scale gene-environment interaction studies.
PLoS ONE 01/2013; 8(1):e54331. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: The limited ability of common variants to account for the genetic contribution to complex disease has prompted searches for rare variants of large effect, to partly explain the 'missing heritability'. Analyses of genome-wide genotyping data have identified genomic structural variants (GSVs) as a source of such rare causal variants. Recent studies have reported multiple GSV loci associated with risk of obesity. We attempted to replicate these associations by similar analysis of two familial-obesity case-control cohorts and a population cohort, and detected GSVs at 11 out of 18 loci, at frequencies similar to those previously reported. Based on their reported frequencies and effect sizes (OR≥25), we had sufficient statistical power to detect the large majority (80%) of genuine associations at these loci. However, only one obesity association was replicated. Deletion of a 220 kb region on chromosome 16p11.2 has a carrier population frequency of 2×10(-4) (95% confidence interval [9.6×10(-5)-3.1×10(-4)]); accounts overall for 0.5% [0.19%-0.82%] of severe childhood obesity cases (P = 3.8×10(-10); odds ratio = 25.0 [9.9-60.6]); and results in a mean body mass index (BMI) increase of 5.8 kg.m(-2) [1.8-10.3] in adults from the general population. We also attempted replication using BMI as a quantitative trait in our population cohort; associations with BMI at or near nominal significance were detected at two further loci near KIF2B and within FOXP2, but these did not survive correction for multiple testing. These findings emphasise several issues of importance when conducting rare GSV association, including the need for careful cohort selection and replication strategy, accurate GSV identification, and appropriate correction for multiple testing and/or control of false discovery rate. Moreover, they highlight the potential difficulty in replicating rare CNV associations across different populations. Nevertheless, we show that such studies are potentially valuable for the identification of variants making an appreciable contribution to complex disease.
PLoS ONE 01/2013; 8(3):e58048. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the association of aircraft noise with risk of stroke, coronary heart disease, and cardiovascular disease in the general population.
Small area study.
12 London boroughs and nine districts west of London exposed to aircraft noise related to Heathrow airport in London.
About 3.6 million residents living near Heathrow airport. Risks for hospital admissions were assessed in 12 110 census output areas (average population about 300 inhabitants) and risks for mortality in 2378 super output areas (about 1500 inhabitants).
Risk of hospital admissions for, and mortality from, stroke, coronary heart disease, and cardiovascular disease, 2001-05.
Hospital admissions showed statistically significant linear trends (P<0.001 to P<0.05) of increasing risk with higher levels of both daytime (average A weighted equivalent noise 7 am to 11 pm, LAeq,16h) and night time (11 pm to 7 am, Lnight) aircraft noise. When areas experiencing the highest levels of daytime aircraft noise were compared with those experiencing the lowest levels (>63 dB v ≤51 dB), the relative risk of hospital admissions for stroke was 1.24 (95% confidence interval 1.08 to 1.43), for coronary heart disease was 1.21 (1.12 to 1.31), and for cardiovascular disease was 1.14 (1.08 to 1.20) adjusted for age, sex, ethnicity, deprivation, and a smoking proxy (lung cancer mortality) using a Poisson regression model including a random effect term to account for residual heterogeneity. Corresponding relative risks for mortality were of similar magnitude, although with wider confidence limits. Admissions for coronary heart disease and cardiovascular disease were particularly affected by adjustment for South Asian ethnicity, which needs to be considered in interpretation. All results were robust to adjustment for particulate matter (PM10) air pollution, and road traffic noise, possible for London boroughs (population about 2.6 million). We could not distinguish between the effects of daytime or night time noise as these measures were highly correlated.
High levels of aircraft noise were associated with increased risks of stroke, coronary heart disease, and cardiovascular disease for both hospital admissions and mortality in areas near Heathrow airport in London. As well as the possibility of causal associations, alternative explanations such as residual confounding and potential for ecological bias should be considered.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Long-term physical inactivity seems to cause many health problems. We studied whether persistent physical activity compared to inactivity has a global effect on serum metabolome towards reduced cardio-metabolic disease risk. METHODS AND RESULTS: Sixteen same-sex twin pairs (mean age 60 yrs) were selected from a cohort of twin pairs on the basis of their over 30-year discordance for physical activity. Persistently (≥5 years) active and inactive groups in three population-based cohorts (mean ages 31 to 52 years) were also studied (1037 age- and sex-matched pairs). Serum metabolome was quantified by nuclear magnetic resonance spectroscopy. We used permutation analysis to estimate significance of the multivariate effect combined across all metabolic measures; univariate effects were estimated by paired testing in twins as well as in matched pairs, in the cohorts, and by meta-analysis over all sub-studies. Persistent physical activity was associated with the multivariate metabolic profile in the twins (P=0.003), and a similar pattern was observed in all three population cohorts with differing mean ages. Isoleucine, α1-acid glycoprotein and glucose were lower in the physically active than in the inactive individuals (P<0.001 in meta-analysis), serum fatty acid composition was shifted towards a less saturated profile, and lipoprotein subclasses towards lower VLDL (P<0.001) and higher large and very large HDL (P<0.001) particle concentrations. The findings persisted after adjustment for body-mass index. CONCLUSIONS: The numerous differences found between persistently physically active and inactive individuals in the circulating metabolome coherently indicate better metabolic health in the physically active than in inactive individuals.
[show abstract][hide abstract] ABSTRACT: The firing of mesolimbic dopamine neurons is important for drug-induced reinforcement, although underlying genetic factors remain poorly understood. In a recent genome-wide association metaanalysis of alcohol intake, we identified a suggestive association of SNP rs26907 in the ras-specific guanine-nucleotide releasing factor 2 (RASGRF2) gene, encoding a protein that mediates Ca(2+)-dependent activation of the ERK pathway. We performed functional characterization of this gene in relation to alcohol-related phenotypes and mesolimbic dopamine function in both mice and adolescent humans. Ethanol intake and preference were decreased in Rasgrf2(-/-) mice relative to WT controls. Accordingly, ethanol-induced dopamine release in the ventral striatum was blunted in Rasgrf2(-/-) mice. Recording of dopamine neurons in the ventral tegmental area revealed reduced excitability in the absence of Ras-GRF2, likely because of lack of inhibition of the I(A) potassium current by ERK. This deficit provided an explanation for the altered dopamine release, presumably linked to impaired activation of dopamine neurons firing. Functional neuroimaging analysis of a monetary incentive-delay task in 663 adolescent boys revealed significant association of ventral striatal activity during reward anticipation with a RASGRF2 haplotype containing rs26907, the SNP associated with alcohol intake in our previous metaanalysis. This finding suggests a link between the RASGRF2 haplotype and reward sensitivity, a known risk factor for alcohol and drug addiction. Indeed, follow-up of these same boys at age 16 y revealed an association between this haplotype and number of drinking episodes. Together, these combined animal and human data indicate a role for RASGRF2 in the regulation of mesolimbic dopamine neuron activity, reward response, and alcohol use and abuse.
Proceedings of the National Academy of Sciences 12/2012; · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
[show abstract][hide abstract] ABSTRACT: Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.
[show abstract][hide abstract] ABSTRACT: We describe a new multivariate statistical approach to recover metabolite structure information from multiple (1)H NMR spectra in population sample sets. SubseT Optimization by Reference Matching (STORM) was developed to select subsets of 1H NMR spectra that contain specific spectroscopic signatures of biomarkers differentiating between different human populations. STORM aims to improve the visualization of structural correlations in spectroscopic data using these reduced spectral subsets containing smaller numbers of samples than the number of variables (n≪p). We have used 'statistical shrinkage' to limit the number of false positive associations and to simplify the overall interpretation of the auto-correlation matrix. The STORM approach has been applied to findings from an on-going human Metabolome-Wide Association study on Body Mass Index to identify a biomarker metabolite present in a subset of the population. Moreover, we have shown how STORM improves the visualization of more abundant NMR peaks compared to a previously published method (STOCSY). STORM is a useful new tool for biomarker discovery in the 'omic' sciences that has a widespread applicability. It can be applied to any type of data, provided that there is interpretable correlation among variables, and can also be applied to data with more than 1 dimension (e.g. 2D-NMR spectra).
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Cardiovascular disease (CVD) mortality has more than halved in England since the 1980s, but there are few data on small-area trends. We estimated CVD mortality by ward in 5-year intervals between 1982 and 2006, and examined trends in relation to starting mortality, region and community deprivation. METHODS: We analysed CVD death rates using a Bayesian spatial technique for all 7932 English electoral wards in consecutive 5-year intervals between 1982 and 2006, separately for men and women aged 30-64 years and ≥65 years. RESULTS: Age-standardized CVD mortality declined in the majority of wards, but increased in 186 wards for women aged ≥65 years. The decline was larger where starting mortality had been higher. When grouped by deprivation quintile, absolute inequality between most- and least-deprived wards narrowed over time in those aged 30-64 years, but increased in older adults; relative inequalities worsened in all four age-sex groups. Wards with high CVD mortality in 2002-06 fell into two groups: those in and around large metropolitan cities in northern England that started with high mortality in 1982-86 and could not 'catch up', despite impressive declines, and those that started with average or low mortality in the 1980s but 'fell behind' because of small mortality reductions. CONCLUSIONS: Improving population health and reducing health inequalities should be treated as related policy and measurement goals. Ongoing analysis of mortality by small area is essential to monitor local effects on health and health inequalities of the public health and healthcare systems.
International Journal of Epidemiology 11/2012; · 6.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: A nutrient-wide approach may be useful comprehensively to test and validate associations between nutrients (derived from foods and supplements) and blood pressure (BP) in an unbiased manner. METHODS AND RESULTS: Data from 4,680 participants ages 40-59 in the cross-sectional International Study of Macro/Micro-nutrients and Blood Pressure (INTERMAP) were stratified randomly into training and testing sets. NHANES cross-sectional cohorts of 1999-2000 to 2005-2006 were used for external validation. We performed multiple linear regression analyses associating each of 82 nutrients and 3 urine electrolytes with systolic and diastolic BP in the INTERMAP training set. Significant findings were validated in the INTERMAP testing set and further in the NHANES cohorts (False Discovery Rate <5% in training, p<0.05 for internal and external validation). Among the validated nutrients, alcohol and urinary sodium-to-potassium ratio were directly associated with systolic BP, and dietary phosphorus, magnesium, iron, thiamin, folacin, and riboflavin were inversely associated with systolic BP. In addition, dietary folacin, and riboflavin were inversely associated with diastolic BP. The absolute effect sizes in the validation data (NHANES) ranged from 0.97 mmHg lower systolic BP (phosphorus) to 0.39 mmHg lower systolic BP (thiamin) per 1SD difference in nutrient variable. Inclusion of nutrient intake from supplements in addition to foods gave similar results for some nutrients, though it attenuated the associations of folacin, thiamin and riboflavin intake with BP. CONCLUSIONS: We identified significant inverse associations between B vitamins and BP, relationships hitherto poorly investigated. Our analyses represent a systematic unbiased approach to the evaluation and validation of nutrient-BP associations.