Maternal and offspring FADS polymorphisms, dietary LC-PUFAs, and adolescent cardiometabolic health

母体和后代 FADS 多态性、膳食 LC-PUFA 和青少年心脏代谢健康

• 批准号: 10701686
• 负责人: Sonia Tandon
• 金额: $ 4.77万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10701686
• 关键词: 11 year old; Address; Adolescent; Adult; Affect; Age; Alleles; Animal Model; Arachidonic Acids; Area; Bioinformatics; Biological Markers; Birth; Birth Weight; Blood Pressure; Body Composition; Cardiometabolic Disease; Child; Childhood; Chronic Disease; Collaborations; Communication; Complement; Data; Data Set; Development; Diet; Dietary Fatty Acid; Dietary Intervention; Dimensions; Disease; Docosahexaenoic Acid n-3; Docosahexaenoic Acids; Docosahexaenoic acid supplementation; Early Intervention; Early identification; Eicosapentaenoic Acid; Ethnic Origin; European; Exposure to; Fatty Acid Desaturases; Fellowship; Food Interactions; Future; Gene Frequency; Gene Modified; Genes; Genetic; Genetic Polymorphism; Genotype; Goals; Growth and Development function; Haplotypes; Health; Hypertension; Individual; Inflammation; Insulin Resistance; Intake; Intervention; Investigation; Life Cycle Stages; Lipids; Long-Term Effects; Longitudinal cohort; Measures; Mentors; Metabolic; Mexican; Mexico; Modification; Mothers; Native Americans; Nutritional; Nutritional Study; Obesity; Omega-3 Fatty Acids; Omega-6 Fatty Acids; Outcome; Polyunsaturated Fatty Acids; Population; Population Heterogeneity; Precision Health; Pregnancy; Race; Randomized, Controlled Trials; Recommendation; Reporting; Research; Risk Factors; Role; Selection Bias; Strategic Planning; Supplementation; Techniques; Testing; Training; United States National Institutes of Health; Variant; Woman; Work; cardiometabolism; cardioprotection; critical period; dietary; dietary requirement; disorder risk; early adolescence; effective intervention; fatty acid supplementation; follow-up; genetic analysis; genetic approach; genetic information; genetic variant; improved; innovation; metabolic profile; metabolome; mortality; nutrition; offspring; placebo group; pre-doctoral; prenatal; prevent; study population; systematic review; treatment group; western diet

PROJECT SUMMARY Through this predoctoral fellowship, I will obtain in-depth training in life course approaches to improve cardiometabolic health (CMH), analysis of nutrition interventions and longitudinal cohorts, bioinformatics approaches for genetic analysis, and scientific communication. Risk factors for cardiometabolic disease, the leading global cause of mortality, are emerging earlier in the life course, among young children and adolescents. It is therefore critical to identify early and effective intervention strategies. Polyunsaturated fatty acids (PUFAs) have a cardioprotective role as precursors to the long-chain PUFAs (LC-PUFAs) n-6 Arachidonic Acid (AA), n-3 Eicosapentaenoic Acid (EPA) and n-3 Docosahexaenoic Acid (DHA), which modulate inflammation. However, gaps remain in our understanding of the role of LC-PUFAs during critical periods of growth and development, such as gestation and early adolescence, for later CMH. Currently, the long-term effects of prenatal DHA supplementation remain understudied. Inconsistent results across studies may be attributable to population heterogeneity in variants of the fatty acid desaturase (FADS) genes that regulate the conversion of n-3 and n-6 precursors into their LC-PUFA forms. The majority of studies incorporating genetic information have been conducted in European populations, but racial/ethnic variation in the genotype distribution of FADS variants warrants further research. To address these gaps, we will use data from a prenatal DHA supplementation trial (POSGRAD, NCT00646360) conducted in collaboration with Instituto Nacional de Salud Pública (INSP) in Mexico. Mother-child pairs have been followed since birth; most recently, data on maternal and offspring genetics, diet, body composition, and biological markers were collected from offspring at age 11 years. With the support of my mentors, I will use this unique dataset to address the following specific aims: 1) Determine the effect of prenatal DHA supplementation on offspring CMH profiles during early adolescence (n=485) and investigate effect modification by variants in maternal FADS genes (n = 396) and 2) Examine whether variants in offspring FADS genes are associated with CMH profiles in a study population with low intake of n-3 fatty acids (n = 285). I will use measures of lipids, blood pressure, adiposity, insulin resistance, and inflammation to assess CMH profiles. I hypothesize that variants in FADS genes modify the role of dietary LC- PUFAs during gestation and early adolescence on CMH among Mexican adolescents. By addressing these complementary aims, we will significantly advance understanding of gene-nutrient interactions during critical periods of growth and development in a population that has typically been understudied. Through completion of this work, I will develop expertise in innovative approaches including dimensionality reduction techniques to characterize CMH, haplotype estimation, and approaches to address missing data and selection bias due to loss to follow-up. The proposed work complements the 2020-2030 NIH Nutrition Research Strategic Plan, which emphasizes use of precision health approaches to define the role of nutrition across the life course.

项目总结通过此次博士后奖学金，我将获得人生历程的深入训练 改善心脏代谢健康(CMH)的方法，营养干预和纵向队列分析， 用于遗传分析和科学交流的生物信息学方法。心脏代谢异常的危险因素 疾病是全球主要的死亡原因，在生命过程中更早出现，在幼儿和 青少年。因此，确定早期有效的干预战略至关重要。多不饱和脂肪 酸(PUFAs)作为长链PUFAs(LC-PUFAs)n-6花生四烯酸的前体具有心脏保护作用 酸(AA)、n-3二十碳五烯酸(EPA)和n-3二十二碳六烯酸(DHA) 发炎。然而，在#年的关键时期，我们对LC-PUFA作用的理解仍然存在差距。 生长发育，如妊娠和青春期早期，为以后的CMH。目前，长期的 产前补充DHA的效果仍未得到充分研究。不同研究的结果可能不一致 可归因于调节细胞周期的脂肪酸去饱和酶(FADS)基因变异的群体异质性 将n-3和n-6前体转化为其LC-PUFA形式。大多数研究都包含了基因 已经在欧洲人群中进行了信息，但基因分布的种族/民族差异 时尚的变种值得进一步研究。为了解决这些差距，我们将使用产前DHA的数据 与国家Salud研究所合作进行的补充试验(POSGRAD，NCT00646360) 墨西哥的Pública(Insp)。母婴配对从出生起就被跟踪；最近，关于产妇的数据 他们从11岁的孩子身上收集了他们的后代的遗传、饮食、身体成分和生物标记 好几年了。在我导师的支持下，我将使用这个独特的数据集来解决以下具体目标：1) 确定产前补充DHA对青春期早期子代CMH谱的影响 (n=485)和研究母体FADS基因变异的效应修饰(n=396)和2)检查 在低摄入量研究人群中，后代FADS基因变异是否与CMH谱相关 N-3脂肪酸(n=285)。我将使用血脂、血压、肥胖症、胰岛素抵抗和 炎症，以评估CMH的特征。我假设FADS基因的变异改变了饮食中LC的作用。 墨西哥青少年中孕期和青春期早期CMH上的多不饱和脂肪酸。通过解决这些问题 相辅相成的目标，我们将显著提高对关键时期基因-营养相互作用的理解 通常未被充分研究的种群的生长和发展阶段。通过完成 在这项工作中，我将发展创新方法方面的专业知识，包括降维技术 描述CMH、单倍型估计以及解决丢失数据和因丢失而导致的选择偏差的方法 继续跟进。拟议的工作是对2020-2030年美国国立卫生研究院营养研究战略计划的补充，该战略计划 强调使用精确的健康方法来确定营养在整个生命过程中的作用。