Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10−8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5–18.2 mmHg, P = 2.22 × 10−126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54–9.70; P = 4.13 × 10−44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781–0.801) to 0.826 (95% CI, 0.817–0.836, ∆AUROC, 0.035, P = 1.98 × 10−34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men &lt;= 50y, men &gt; 50y, women &lt;= 50y, women &gt; 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR&lt; 5%) age-specific effects, of which 11 had larger effects in younger (&lt; 50y) than in older adults (&gt;= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.</p

Vitaminas antioxidantes e prevenção da arteriosclerose na infância Antioxidant vitamins and prevention of atherosclerosis in childhood

OBJETIVO: Revisar os potenciais efeitos antioxidantes das vitaminas A, C e E na prevenção do desenvolvimento da arteriosclerose na infância, com ênfase na prevenção da dislipidemia. FONTES DE DADOS: Pesquisa bibliográfica em revistas científicas, livros técnicos e publicações de órgãos oficiais dos últimos 20 anos. Utilizaram-se as bases de dados Lilacs, SciELo e Medline em português, inglês e espanhol, com as palavras-chave: "antioxidantes", "arteriosclerose", "dislipidemias", "peroxidação de lipídeos", "infância", "vitamina A", "vitamina C" e "vitamina E". SÍNTESE DE DADOS: A prevalência de dislipidemia na infância e na adolescência mostra frequência crescente, provavelmente relacionada às mudanças dos hábitos alimentares e à redução na prática de atividades físicas. O elevado nível plasmático da lipoproteína de baixa densidade (LDL-c) é fator de risco para o desenvolvimento da arteriosclerose. O consumo de frutas, verduras e legumes, ricos em antioxidantes, é um dos fatores de maior importância na prevenção da peroxidação lipídica. A baixa ingestão dessas fontes naturais de antioxidantes sugere a necessidade de intervenção nutricional para atingir as metas diárias de consumo de vitaminas A, C e E, não sendo preconizada a sua suplementação medicamentosa. CONCLUSÕES: O pediatra e o nutricionista devem orientar as famílias sobre o consumo de alimentos saudáveis, principalmente frutas, verduras e legumes, por seu potencial efeito antioxidante, especialmente nos primeiros anos de vida.<br>OBJECTIVE: To review the potential antioxidant effects of vitamins A, C and E in the prevention of atherosclerosis development during childhood, emphasizing the prevention of dyslipidemia. DATA SOURCES: Bibliographic search in scientific journals, technical books and official publications of the last 20 years. Lilacs, SciElo and Medline databases were searched for articles in Portuguese, Spanish and English using a combination of the following terms: "antioxidants", "atherosclerosis", "dyslipidemia", "lipid peroxidation", "childhood", "vitamin A", "vitamin C" and "vitamin E". DATA SYNTHESIS: There is an increasing prevalence of dyslipidemia in children and adolescents, probably related to changes in dietary habits and to the reduced practice of physical activities. The high plasma concentration of low-density lipoprotein (LDL-c) is a risk factor for atherosclerosis development. The consumption of nutrients rich in antioxidants, such as fruits and vegetables, is very important to prevent lipid peroxidation. The low intake of these natural antioxidants sources suggests the need for nutritional intervention to achieve the daily ingestion targets of vitamins A, C and E. Vitamin supplementation is not recommended. CONCLUSIONS: Children should be encouraged to increase ingestion of fruits and vegetables due to their potential antioxidant effect, especially in the first years of life

Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits

\ua9 2024. The Author(s). Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P &lt; 5 7 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 7 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 7 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 7 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research