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Jeffrey R Gruen, MD

Professor of Pediatrics (Neonatology) and of Genetics
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Additional Titles

Faculty, Investigative Medicine Program, Yale Graduate School of Arts and Sciences

About

Titles

Professor of Pediatrics (Neonatology) and of Genetics

Faculty, Investigative Medicine Program, Yale Graduate School of Arts and Sciences

Biography

Dr. Gruen received his BS and his MD degrees from Tulane University in New Orleans. He has been at Yale since beginning internship training in pediatrics in 1981, which was followed by subspecialty training in neonatology and research training in molecular genetics with Dr. Sherman Weissman. Dr. Gruen formally joined the faculty at Yale in 1988, splitting his time as a neonatology attending in the Newborn Intensive Care Unit (NICU) at Yale-New Haven Hospital and his lab where he initially mapped the gene for hemochromatosis. By 2000, the focus of his lab turned to mapping and identifying the reading disability (dyslexia) gene locus on chromosome 6 (DYX2). His lab was the first to generate high-resolution genetic markers, genetic association maps, and gene expression maps of DYX2. These studies led to the identification of DCDC2, a dyslexia gene that was cited by the journal Science as the 5th top breakthrough of 2005. The lab performed an NIH funded clinical study of DCDC2 and other genes related to reading and language in the ALSPAC birth cohort of 10,000 children and mothers. These studies identified the transcriptional control element called READ1, and READ1 alleles that are detrimental and protective for reading disability and language impairment. Dr. Gruen is the principal investigator for the Yale Genes, Reading and Dyslexia (GRaD) Study, a ground-breaking case-control study of dyslexia in 1,400 Hispanic American and African American children recruited from seven sites across North America. He was the Yale site PI for the NIH Pediatric Imaging NeuroGenetics (PING) Data Resource Study of 1,575 normal children, ages 3-20 years. Most recently, Dr. Gruen started the New Haven Lexinome Project, a new six-year longitudinal study of the genetics of response-to-intervention spanning the entire 2015 and 2016 New Haven Public Schools first grade classes. The goals of the New Haven Lexinome Project are to determine risk for learning disabilities conferred by specific genetic variants for presymptomatic diagnosis, and to determine how genetic variants inform intervention for precision/personal education. In addition to his research, Dr. Gruen continues to attend 8 weeks each year in the NICU at the Children’s Hospital at Yale-New Haven.

How genes can change language. Short video showing how our genes could account for a substantial amount of the diversity of languages around the world

Appointments

Education & Training

Fellow
Yale University School of Medicine, New Haven, CT (1988)
Resident
Yale-New Haven Hospital, New Haven, CT (1984)
Intern
Pediatrics, Yale-New Haven Hospital, New Haven, CT (1982)
MD
Tulane University (1981)
BS
Tulane University, Chemistry (1977)

Research

Overview

Projects

Human Genetic Studies: We use human genetic methods such as genetic association and sequencing studies to identify specific genes and genetic elements that contribute to dyslexia and language impairment. Methods range from specific interrogation of the DYX2 risk locus on chromosome 6p22 with a dense marker panel, to hypothesis-free methods such as genome-wide association and sequencing studies. We have collaborated with groups across the country and internationally to ascertain and collect subjects. Ongoing collaborations include the Avon Longitudinal Study of Parents and Children (ALSPAC) at the University of Bristol (UK), the Colorado Learning Disabilities Research Center at the University of Colorado-Boulder, The Child Language Research Center at the University of Iowa, Case Western Reserve University, as well as numerous other national and international collaborators. Our goal for these studies is to identify genetic elements that substantially contribute to reading- and language-related processes in order to (1) gain valuable insight into the mechanisms underlying dyslexia and language impairment—and also into the mechanisms underlying the biology of normal reading and language—and (2) attempt to use genetic information to identify children that may be at risk for communication disorders, in order to apply early intervention and improve the outcome for these individuals.

Molecular Genetic Studies: Our human genetic studies have recently uncovered a synergistic genetic interaction between two risk elements within the DYX2 locus: (1) READ1 (‘regulatory element associated with dyslexia 1’) within intron 2 of DCDC2 and (2) a risk haplotype within KIAA0319, another known dyslexia risk gene in the same locus as DCDC2. Using shift assays, mass spectrometry, and chromatin immunoprecipitation techniques, we determined that the potent transcription factor ETV6 specifically binds the READ1 element. Ongoing studies aim to determine the biological implications of READ1 and its possible regulatory capabilities, within DYX2 and throughout the genome. Future studies are planned to study the biological effects of READ1 alleles in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) that can be differentiated into neural progenitor cells and terminally differentiated neural cells. .

The Yale Genes, Reading and Dyslexia (GRaD) Study: The GRaD Study is a multi-center case/control study of the genetics of dyslexia in Hispanic-American and African-American children. Each child receives an extensive battery of standardized reading, language, IQ, attention, and motivation assessments. We collect DNA from every child in preparation for a genome-wide association study (GWAS) to identify genetic markers informative in understudied populations in the U.S. and Canada. To date we have enrolled over 1100 children from recruitment and testing centers in New Haven, Boston, Toronto, Denver, Boulder, Albuquerque, and Baltimore.

Imaging Genetics (IG): In addition to traditional cognitive assessments, we also perform genetic association with non-invasive brain imaging phenotypes, using magnetic resonance imaging (MRI). We use several MRI protocols, including structural (T2 and diffusion weighted imaging), functional, structural connectivity (fractional anisotropy), and functional connectivity. Subjects for these studies are recruited from the Pediatric Imaging NeuroGenetics (PING) Study, as well as the GRaD Study. The goal of these imaging-genetics studies is to connect risk variants from our neurobehavioral genetic studies to the biological phenotypes observed with high-resolution structural and functional imaging.

Sluggish Cognitive Tempo (SCT): This is a collaborative project with investigators at The Kennedy-Krieger Institute at Johns Hopkins University in Baltimore. The aim of this project is to examine the relationships between neuropsychological skills and candidate gene variants in children ages 8 to 15 years who display slow processing speed in the context of behaviorally defined sluggish cognitive tempo (SCT). [I1] SCT is a collection of symptoms characterized by lethargy, under activity, and slowness, and has been observed in a variety of childhood conditions including attention deficit hyperactivity disorder (ADHD) and dyslexia. SCT and processing speed are considered overlapping yet distinct constructs. Children with ADHD commonly display slowed processing speed; however, slow processing speed is also sometimes observed in dyslexia. Therefore, processing speed and components of SCT may account, in part, for the comorbidity between ADHD and dyslexia.

[I1]I would move this to the end of the paragraph.

Medical Subject Headings (MeSH)

Dyslexia; Genetics; Investigative Techniques; Language; Language Development Disorders; Learning Disabilities; Neonatology; Pediatrics

Research at a Glance

Yale Co-Authors

Frequent collaborators of Jeffrey R Gruen's published research.

Publications

2024

2023

2022

2017

2016

2014

Academic Achievements & Community Involvement

  • honor

    Innovative Research Award

  • activity

    GRaD Study

Clinical Care

Overview

Jeffrey R. Gruen, MD, is a pediatrician specializing in disorders in newborn babies. He treats conditions that typically result from prematurity, congenital genetic disorders, inborn metabolic errors and infections.

In addition to his clinical work, Dr. Gruen has been the principal investigator in a number of notable studies of the genetics of reading disability (dyslexia) and language impairment. “My work focuses on learning disabilities such as dyslexia, language impairment and speech-sound disorder,” he says.

A professor of pediatrics (neonatology) and of genetics at Yale School of Medicine, Dr. Gruen is also a member of the Investigative Medicine Program, a PhD program at Yale School of Medicine. He is an investigator in the Learning Disabilities Research Center at the University of Colorado, Boulder; and a member of the Learning Disabilities Research Centers Consortium funded by the National Institutes of Health.

Clinical Specialties

Neonatal - Perinatal Medicine; Pediatric Genetics

Board Certifications

  • Pediatrics

    Certification Organization
    AB of Pediatrics
    Original Certification Date
    1986

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