Integrative metabolomic characterization of ADHD and asthma comorbidity

ADHD 和哮喘合并症的综合代谢组学特征

• 批准号: 10650374
• 负责人: Su Hee Chu
• 金额: $ 17.82万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10650374
• 关键词: Achievement; Adolescence; Adult; Area; Asthma; Attention deficit hyperactivity disorder; Awareness; Behavior Disorders; Biochemical; Biological; Biological Markers; Child; Childhood; Childhood Asthma; Clinical; Communication; Communities; Complex; Data; Diagnosis; Disease; Doctor of Philosophy; Educational process of instructing; Ensure; Environmental Exposure; Epidemiologist; Epidemiology; Etiology; Formulation; Genetic; Genetic Variation; Goals; Hospitals; Individual; Joints; Libraries; Link; Literature; Longevity; Longitudinal Studies; Machine Learning; Mediating; Mediation; Mediator; Mentored Research Scientist Development Award; Mentors; Mentorship; Metabolic; Metabolic Pathway; Metabolism; Methods; Modeling; Molecular; Multiomic Data; Neurodevelopmental Disorder; Pathway interactions; Patients; Phenotype; Prevalence; Process; Program Development; Prospective Studies; Prospective cohort; Public Health; Reporting; Research; Research Design; Research Personnel; Respiration Disorders; Respiratory Disease; Risk; Specific qualifier value; Sphingolipids; Statistical Methods; System; Techniques; Testing; Training; Tryptophan; Validation; Variant; Vitamin D; Woman; antenatal; asthmatic; asthmatic patient; biological systems; career; career development; cohort; comorbidity; experience; genetic testing; genetic variant; high risk; improved; inattention; insight; medical schools; metabolic phenotype; metabolic profile; metabolomics; method development; multiple omics; novel; predictive modeling; programs; prospective; psychogenetics; research and development; screening; skills; small molecule; statistics; success; theories

PROJECT SUMMARY/ABSTRACT Su H. Chu, PhD, MS is a biostatistician and molecular epidemiologist with strong and substantial commitments to integrative omic research in respiratory and neurodevelopmental disease. Her career objective is to become an independent investigator with expertise in developing and applying novel statistical methods and multiomic network approaches that facilitate mechanistic understanding of the intersection of respiratory and neurodevelopmental disease. This proposal combines Dr. Chu’s extensive training in integrative omic methods development, along with her experience in genetic and metabolomic research, to examine the integrative metabolomic etiology of asthma and attention-deficit/hyperactivity disorder overlap (AAO). A wealth of epidemiological literature has revealed with remarkable consistency that asthmatic patients are at greater risk for ADHD, and vice versa, with a number of longitudinal studies of childhood asthma indicating excess risk of ADHD in adolescence and adulthood. However, no studies have directly interrogated the biological mechanisms by which these conditions may be related. The central hypothesis of this proposal is that childhood asthma and ADHD share both common and distinct dysregulated metabolic processes, some of which may have drivers that are genetic in origin. This will be explored using existing genetic and metabolomic data from the Childhood Asthma Management Program (CAMP), the Vitamin D Antenatal Asthma Reduction Trial (VDAART), and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC), three large prospective cohorts of children with extensive longitudinal phenotyping and multiple omic data types, by identifying metabolites and metabolic profiles associated with AAO (aim 1), constructing multiomic models and features that characterize dysregulated metabolic processes and their upstream drivers in AAO (aim 2), and validation and replication of all findings (aim 3). As Dr. Chu completes these aims, her career development program will facilitate the achievement of her primary training goals: 1) increase clinical understanding of ADHD and asthma diagnosis and treatment; 2) gain a nuanced understanding of best methods for, and practical experience in, the biological and statistical integration of genetic and metabolomic data; 3) develop skills in machine learning and integrative network methods for multiomic analysis; 4) strengthen current areas of experience to stay on the cutting edge of new analytic and study design techniques; and 5) enhance skills in mentorship, teaching, and the responsible conduct and communication of research. The support of a diverse mentoring team comprised of world experts in the fields of asthma and psychiatric genetics, metabolomics, integrative omics, and statistics, along with her strong quantitative training and the vibrant intellectual community of Harvard Medical School and the Brigham and Women’s Hospital, ensure the success of this proposal. Finally, this research will use state-of-the-art multiomic techniques to lay the initial groundwork for understanding the pathobiology of asthma and ADHD comorbidity, a major and well-established public health concern, from which new research programs will emerge.

项目总结/文摘

项目成果

Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma.

• DOI: 10.1038/s41591-022-01714-5
• 发表时间: 2022-04
• 期刊: NATURE MEDICINE
• 影响因子: 82.9
• 作者: Kachroo, Priyadarshini;Stewart, Isobel D.;Kelly, Rachel S.;Stav, Meryl;Mendez, Kevin;Dahlin, Amber;Soeteman, Djora I.;Chu, Su H.;Huang, Mengna;Cote, Margaret;Knilhtila, Hanna M.;Lee-Sarwar, Kathleen;McGeachie, Michael;Wang, Alberta;Wu, Ann Chen;Virkud, Yamini;Zhang, Pei;Wareham, Nicholas J.;Karlson, Elizabeth W.;Wheelock, Craig E.;Clish, Clary;Weiss, Scott T.;Langenberg, Claudia;Lasky-Su, Jessica A.
• 通讯作者: Lasky-Su, Jessica A.

Low gestational vitamin D level and childhood asthma are related to impaired lung function in high-risk children.

妊娠期维生素 D 水平低和儿童哮喘与高危儿童的肺功能受损有关。

• DOI: 10.1016/j.jaci.2020.12.647
• 发表时间: 2021-07
• 期刊: The Journal of allergy and clinical immunology
• 作者: Knihtilä HM;Stubbs BJ;Carey VJ;Laranjo N;Chu SH;Kelly RS;Zeiger RS;Bacharier LB;O'Connor GT;Lasky-Su J;Weiss ST;Litonjua AA
• 通讯作者: Litonjua AA

An independently validated, portable algorithm for the rapid identification of COPD patients using electronic health records.

• DOI: 10.1038/s41598-021-98719-w
• 发表时间: 2021-10-07
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Chu SH;Wan ES;Cho MH;Goryachev S;Gainer V;Linneman J;Scotty EJ;Hebbring SJ;Murphy S;Lasky-Su J;Weiss ST;Smoller JW;Karlson E
• 通讯作者: Karlson E

Metabolomic signatures of lead exposure in the VA Normative Aging Study.

• DOI: 10.1016/j.envres.2020.110022
• 发表时间: 2020-11
• 期刊: Environmental research
• 影响因子: 8.3
• 作者: Kelly RS;Bayne H;Spiro A 2nd;Vokonas P;Sparrow D;Weiss ST;Schwartz J;Nassan FL;Lee-Sarwar K;Huang M;Kachroo P;Chu SH;Litonjua AA;Lasky-Su JA
• 通讯作者: Lasky-Su JA

Nucleotide, Phospholipid, and Kynurenine Metabolites Are Robustly Associated with COVID-19 Severity and Time of Plasma Sample Collection in a Prospective Cohort Study.

在一项前瞻性队列研究中，核苷酸，磷脂和kynurenine代谢物与CoVID-19的严重程度和等离子体样品收集的时间牢固相关。

• DOI: 10.3390/ijms25010346
• 发表时间: 2023-12-26
• 期刊: International journal of molecular sciences
• 影响因子: 5.6