Roel A Ophoff

Roel A. Ophoff, PhD, is Professor-in-Residence at the David Geffen School of Medicine, University of California, Los Angeles (UCLA), holding joint appointments in the Departments of Psychiatry and Biobehavioral Sciences and Human Genetics. Since obtaining his PhD in Human Genetics from Leiden University in 1997, he has led an expansive research program investigating the genetic and genomic underpinnings of psychiatric and neurodegenerative disorders.

Education:

• PhD in Human Genetics, Leiden University, The Netherlands, 1997

Research Focus:

Ophoff’s work integrates large-scale genome-wide association studies (GWAS), whole-genome and exome sequencing, epigenomics, and metabolomics to dissect the biological basis of schizophrenia, bipolar disorder, eating disorders, ALS, and Alzheimer’s disease. His laboratory leverages multi-ethnic cohorts—including under-represented populations through the PUMAS and NeuroGAP-Psychosis consortia—to identify both common and rare genetic variants influencing disease risk, age at onset, and clinical heterogeneity.

Key methodological advances include the development of DNA methylation predictors for pathogenic repeat expansions, cell-type deconvolution of bulk-tissue transcriptomes, and blended sequencing strategies that maximize variant discovery while minimizing cost.

Scientific Output & Impact:

Across more than 250 publications, his recent contributions reveal shared and distinct genetic architectures between bipolar disorder and major depression, novel risk loci for suicide attempt, and the role of fetal neurodevelopmental gene deletions in schizophrenia. These findings have been disseminated in Nature, Nature Genetics, Nature Neuroscience, and the American Journal of Psychiatry, collectively cited thousands of times.

Funding & Current Projects:

• Principal Investigator, NIH R21AG072390: “Improving Prediction of Prognosis in Frontotemporal Dementia Using Epigenetic and Genetic Markers of Biological Aging and Disease” (2021–2023)
• Co-Principal Investigator, NIH U01MH125042: “Powering Genetic Discovery for Severe Mental Illness in Latin American and African Ancestries” (2020–2025)
• Principal Investigator, NIH R01MH114152: “Genetic, Imaging, and Cognition study of Positive Valence Systems in Psychotic Syndromes” (2018–2023)
• Principal Investigator, NIH RF1AG058484: “Genetics of CSF Metabolites in Alzheimer Disease and other Brain Disorders” (2018–2023)
• Principal Investigator, NIH T32NS048004: “Training Grant in Neurobehavioral Genetics” (2004–2026)

Research Environment:

Ophoff directs a multidisciplinary team embedded within UCLA’s Neurobehavioral Genetics Laboratory. The group collaborates closely with the ENIGMA consortium, Psychiatric Genomics Consortium (PGC), TOPMed, and several international biobanks, providing trainees and staff access to cutting-edge computational resources, high-performance clusters, and large-scale genomic datasets exceeding 100,000 individuals.