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<p class="eyebrow">Fritsche Lab · University of Michigan</p>
<h1 id="home-title">We test what genomic and health data can reliably tell us.</h1>
<p class="home-hero__summary">We study prediction models built from genomic data, health records, and patient-reported information. Much of our work begins after a model has been built: we test how well it performs in new populations and health systems, and why performance varies.</p>
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<a class="button button--primary" href="/research/">Research programs</a>
<a class="button button--secondary" href="/tools/">Tools and data</a>
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</div>
<figure class="hero-visual validation-figure">
<div class="validation-figure__heading">Independent evaluation</div>
<div class="validation-figure__cohorts">
<div class="validation-figure__cohort validation-figure__cohort--development">
<div class="validation-figure__label"><strong>Develop</strong></div>
<p class="validation-figure__subhead">One cohort</p>
<svg viewBox="0 0 260 276" role="img" aria-labelledby="development-title development-desc">
<title id="development-title">Model development</title>
<desc id="development-desc">A model curve follows a set of blue observations in the development cohort. These marks are illustrative, not measured results.</desc>
<g class="validation-figure__grid" fill="none">
<path d="M20 58H250 M20 116H250 M20 174H250 M78 26V232 M136 26V232 M194 26V232" />
</g>
<path class="validation-figure__axis" d="M20 26V232H250" fill="none" />
<g class="validation-figure__observations">
<circle cx="29" cy="218" r="3" /><circle cx="34" cy="195" r="3" />
<circle cx="43" cy="226" r="3" /><circle cx="46" cy="203" r="3" />
<circle cx="54" cy="185" r="3" /><circle cx="57" cy="214" r="3" />
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<circle cx="244" cy="65" r="3" />
</g>
<path class="validation-figure__model" d="M24 212 C62 210 82 195 104 171 S147 109 172 90 S216 59 246 55" fill="none" />
</svg>
</div>
<div class="validation-figure__cohort validation-figure__cohort--evaluation">
<div class="validation-figure__label"><strong>Test</strong></div>
<p class="validation-figure__subhead">An independent cohort</p>
<svg viewBox="0 0 260 276" role="img" aria-labelledby="validation-title validation-desc">
<title id="validation-title">Independent evaluation</title>
<desc id="validation-desc">The identical model curve is tested against a different set of teal observations. Fine vertical lines mark selected differences between the model and observations. These marks are illustrative, not measured results.</desc>
<g class="validation-figure__grid" fill="none">
<path d="M20 58H250 M20 116H250 M20 174H250 M78 26V232 M136 26V232 M194 26V232" />
</g>
<path class="validation-figure__axis" d="M20 26V232H250" fill="none" />
<g class="validation-figure__differences" fill="none">
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</g>
<g class="validation-figure__observations">
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<path class="validation-figure__model" d="M24 212 C62 210 82 195 104 171 S147 109 172 90 S216 59 246 55" fill="none" />
</svg>
</div>
</div>
<figcaption>
<span class="validation-figure__key">Same model. New people.</span>
<span class="validation-figure__note">Conceptual illustration</span>
</figcaption>
</figure>
</div>
</section>
<div class="evidence-strip" role="group" aria-label="How we work">
<div class="evidence-strip__inner">
<div class="evidence-strip__item"><strong>Independent evaluation</strong><span>Testing models with data that were not used to build them</span></div>
<div class="evidence-strip__item"><strong>Longitudinal context</strong><span>Linking genomics with health records and patient reports</span></div>
<div class="evidence-strip__item"><strong>Reusable results</strong><span>Publishing methods, score files, mappings, and comparisons</span></div>
<div class="evidence-strip__item"><strong>Team science</strong><span>Working with clinical, statistical, and computational colleagues</span></div>
</div>
</div>
<section class="home-section" aria-labelledby="programs-title">
<div class="section-heading">
<div><p class="eyebrow">Research</p><h2 id="programs-title">Do findings hold up in a new setting?</h2><p>This question connects our work in polygenic risk, biobanks linked to electronic health records (EHRs), mental health, and pain.</p></div>
<a class="text-link" href="/research/">Research overview →</a>
</div>
<div class="card-grid card-grid--four">
<article class="lab-card lab-card--linked research-card program-card--polygenic-risk" id="scalable-prs">
<p class="card-kicker">Polygenic risk</p>
<h3><a class="card-primary-link" href="/research/polygenic-risk/">Evaluating Polygenic Risk Scores at Scale <span class="card-link-arrow" aria-hidden="true">→</span></a></h3>
<p class="card-summary">We test published risk scores in large biobanks and release the results, methods, mappings, and score files.</p>
</article>
<article class="lab-card lab-card--linked research-card program-card--ehr-biobanks" id="ehr-linked-biobanks">
<p class="card-kicker">Biobanks</p>
<h3><a class="card-primary-link" href="/research/ehr-linked-biobanks/">Biobanks Linked to Electronic Health Records <span class="card-link-arrow" aria-hidden="true">→</span></a></h3>
<p class="card-summary">We link genomic data with health records collected over time to study disease patterns, treatment, and outcomes.</p>
</article>
<article class="lab-card lab-card--linked research-card program-card--mental-health" id="precision-mental-health">
<p class="card-kicker">Mental health</p>
<h3><a class="card-primary-link" href="/research/precision-mental-health/">Precision Mental Health <span class="card-link-arrow" aria-hidden="true">→</span></a></h3>
<p class="card-summary">We study mental health treatment response using genetic, clinical, and patient-reported data.</p>
</article>
<article class="lab-card lab-card--linked research-card program-card--pain-genetics-phenotyping" id="pain-genetics-phenotyping">
<p class="card-kicker">Pain research</p>
<h3><a class="card-primary-link" href="/research/pain-genetics-phenotyping/">Nociplastic Pain: Phenotyping and Genetics <span class="card-link-arrow" aria-hidden="true">→</span></a></h3>
<p class="card-summary">We study nociplastic pain and overlapping chronic pain conditions using patient-reported information, health records, and statistical genetics.</p>
</article>
</div>
</section>
<section class="home-section" aria-labelledby="impact-title">
<div class="feature-panel">
<div class="feature-panel__copy">
<p class="eyebrow">Current collaboration · Precision mental health</p>
<h2 id="impact-title">Why does the same mental health treatment help one person more than another?</h2>
<p>COMPASS studies treatment response using genetic, clinical, and patient-reported information. The principal investigators are Amy Bohnert, Srijan Sen, and Lars Fritsche. Lars leads the genetics and EHR data work.</p>
<div class="button-row">
<a class="button button--primary" href="/research/precision-mental-health/">About the research</a>
<a class="button button--secondary" href="https://medschool.umich.edu/news-release/trial-and-error-targeted-precision-179m-grant-accelerates-u-m-mental-health-research">U-M project story <span aria-hidden="true">↗</span></a>
</div>
</div>
<div class="feature-panel__visual feature-panel__visual--study">
<picture class="theme-image theme-image--light">
<source media="(max-width: 40rem)" srcset="/assets/images/programs/precision-mental-health-mobile.svg" width="400" height="600" />
<img src="/assets/images/programs/precision-mental-health.svg" alt="Conceptual study design combining genetic data, clinical and treatment history, and patient reports to study mental health treatment response over time. Trajectories are illustrative. Models are tested in a separate dataset when suitable data are available." width="720" height="480" loading="lazy" />
</picture>
<picture class="theme-image theme-image--dark">
<source media="(max-width: 40rem)" srcset="/assets/images/programs/precision-mental-health-mobile.svg#dark" width="400" height="600" />
<img src="/assets/images/programs/precision-mental-health.svg#dark" alt="Conceptual study design combining genetic data, clinical and treatment history, and patient reports to study mental health treatment response over time. Trajectories are illustrative. Models are tested in a separate dataset when suitable data are available." width="720" height="480" loading="lazy" />
</picture>
</div>
</div>
</section>
<section class="home-section" aria-labelledby="prsweb-title">
<div class="section-heading">
<div><p class="eyebrow">Research resource</p><h2 id="prsweb-title">Compare published polygenic risk scores across biobanks</h2><p>PRSweb reports how published scores performed in the Michigan Genomics Initiative and UK Biobank. The three archived releases remain unchanged, so their results and source files continue to match the papers that describe them.</p></div>
</div>
<div class="feature-panel feature-panel--resource">
<div class="feature-panel__copy">
<p class="eyebrow">PRSweb Research Portals</p>
<h2>Scores, comparisons, and source files in one place</h2>
<p>Each release includes performance results, phenome-wide associations, phenotype mappings, methods, and downloadable score files.</p>
<div class="resource-access">
<div class="button-row">
<a class="button button--primary" href="https://csg.sph.umich.edu/larsf/">Open PRSweb <span aria-hidden="true">↗</span></a>
<a class="button button--secondary" href="/tools/prsweb/" aria-label="Resource details: PRSweb Research Portals">Resource details</a>
</div>
<div class="resource-release-links">
<p>Open an archived portal</p>
<ul><li><a href="https://csg.sph.umich.edu/larsf/skincancerprsweb/"><span class="resource-name"><img class="resource-icon" src="/assets/images/resources/skincancerprsweb.svg" width="32" height="32" alt="" aria-hidden="true" /><span>Skin Cancer PRSweb (2019) <span aria-hidden="true">↗</span></span></span></a></li>
<li><a href="https://csg.sph.umich.edu/larsf/cancerprsweb/"><span class="resource-name"><img class="resource-icon" src="/assets/images/resources/cancerprsweb.svg" width="32" height="32" alt="" aria-hidden="true" /><span>Cancer PRSweb (2020) <span aria-hidden="true">↗</span></span></span></a></li>
<li><a href="https://csg.sph.umich.edu/larsf/exprsweb/"><span class="resource-name"><img class="resource-icon" src="/assets/images/resources/exprsweb.svg" width="32" height="32" alt="" aria-hidden="true" /><span>ExPRSweb (2021) <span aria-hidden="true">↗</span></span></span></a></li></ul>
</div>
</div>
</div>
<div class="feature-panel__visual">
<img src="/assets/images/resources/prsweb-portal.png" alt="The PRSweb landing page with Fritsche Lab branding, cross-portal trait search, and links to Skin Cancer PRSweb, Cancer PRSweb, and ExPRSweb." width="1440" height="1020" loading="lazy" />
</div>
</div>
</section>
<section class="home-section" aria-labelledby="tools-title">
<div class="section-heading">
<div><p class="eyebrow">Software and teaching</p><h2 id="tools-title">Tools for reproducible research</h2><p>Software, practical guides, and teaching materials for data analysis, cluster computing, and coding.</p></div>
<a class="text-link" href="/tools/">All tools and data →</a>
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<article class="lab-card resource-card accent-teal" id="resource-phewasflow">
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<p class="card-kicker">PheWAS software</p>
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<h3>phewasFlow</h3>
<p class="card-summary">An R package for reproducible phenome-wide association studies in both directions, with local and cluster workflows, multiple-testing correction, and Manhattan and volcano plots.</p>
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<a class="button button--primary" href="https://github.com/FritscheLab/phewasFlow">View phewasFlow on GitHub <span aria-hidden="true">↗</span></a>
<a class="button button--secondary" href="/tools/phewasflow/" aria-label="Resource details: phewasFlow">Resource details</a>
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</article>
<article class="lab-card resource-card accent-maize" id="resource-slurm-playbook">
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<p class="card-kicker">Research computing guide</p>
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<h3>Fritsche Lab SLURM Playbook</h3>
<p class="card-summary">The SLURM Playbook covers submitting and monitoring CPU jobs and job arrays on U-M clusters, diagnosing failures, and rerunning only failed tasks.</p>
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<a class="button button--primary" href="https://fritschelab.org/slurm-playbook/">Open the SLURM Playbook <span aria-hidden="true">↗</span></a>
<a class="button button--secondary" href="/tools/slurm-playbook/" aria-label="Resource details: Fritsche Lab SLURM Playbook">Resource details</a>
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<article class="lab-card resource-card accent-teal" id="resource-practical-genai-coding-guide">
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<p class="card-kicker">Practical GenAI · Part 1</p>
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<h3>Practical GenAI Coding Guide</h3>
<p class="card-summary">An eight-step workflow for AI-assisted research code, covering planning, prompting, review, testing, version control, and documentation.</p>
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<a class="button button--primary" href="https://fritschelab.org/practical-genai-coding-guide/">Read the 8-step guide <span aria-hidden="true">↗</span></a>
<a class="button button--secondary" href="/tools/practical-genai/" aria-label="Resource details: Practical GenAI Coding Guide">Resource details</a>
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<article class="lab-card resource-card accent-teal" id="resource-practical-genai-agentic-coding-guide">
<div class="card-heading-row">
<p class="card-kicker">Practical GenAI · Part 2</p>
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<h3>Practical GenAI Agentic Coding Guide</h3>
<p class="card-summary">Six lessons for working with coding agents in a runnable research repository, from a task brief through implementation, testing, review, and handoff.</p>
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<a class="button button--primary" href="https://fritschelab.org/practical-genai-agentic-coding-guide/docs/quickstart.html">Start with the demo <span aria-hidden="true">↗</span></a>
<a class="button button--secondary" href="/tools/practical-genai-agentic/" aria-label="Resource details: Practical GenAI Agentic Coding Guide">Resource details</a>
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</section>
<section class="home-section" aria-labelledby="publications-title">
<div class="section-heading">
<div><p class="eyebrow">Selected research</p><h2 id="publications-title">Papers from our current and earlier work</h2></div>
<a class="text-link" href="/publications/">Publications →</a>
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<div class="publication-list">
<article class="publication-item" id="immune-checkpoint-thyroid-toxicity-prs-2026">
<div class="publication-year"><span class="visually-hidden">Published </span>2026</div>
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<h3>Polygenic Risk Scores for Prediction of Immune Checkpoint Inhibitor Thyroid Toxicity in Diverse Populations</h3>
<p class="publication-venue">Clinical Cancer Research</p>
<p class="publication-significance"><strong>Why it matters:</strong> Treatment-related outcomes include adverse effects as well as benefits. In 4,289 veterans treated with checkpoint inhibitors, an updated hypothyroidism polygenic score predicted thyroiditis in both the non-Hispanic White and Black patient groups, but not in chemotherapy controls. The older score, which was derived from European-ancestry data, did not predict thyroiditis in the Black patient group. This shows why scores need to be validated in each population and treatment setting.</p>
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<a href="https://doi.org/10.1158/1078-0432.CCR-26-0620" target="_blank" rel="noopener noreferrer" aria-label="DOI: Polygenic Risk Scores for Prediction of Immune Checkpoint Inhibitor Thyroid Toxicity in Diverse Populations">DOI</a>
<a href="https://pubmed.ncbi.nlm.nih.gov/42240401/" target="_blank" rel="noopener noreferrer" aria-label="PubMed: Polygenic Risk Scores for Prediction of Immune Checkpoint Inhibitor Thyroid Toxicity in Diverse Populations">PubMed</a>
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</div>
</article>
<article class="publication-item" id="prostate-prs-clinical-utility-2025">
<div class="publication-year"><span class="visually-hidden">Published </span>2025</div>
<div>
<h3>Assessing the Clinical Utility of Published Prostate Cancer Polygenic Risk Scores in a Large Biobank Data Set</h3>
<p class="publication-venue">European Urology Oncology</p>
<p class="publication-significance"><strong>Why it matters:</strong> Researchers tested 16 published prostate cancer scores in the Michigan Genomics Initiative (MGI) and used detailed biopsy data to evaluate their clinical utility. Even the best-performing score separated cases from controls only modestly, and none distinguished aggressive from indolent disease. Predicting a diagnosis is not the same as identifying the cancers that most need treatment.</p>
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<a href="https://doi.org/10.1016/j.euo.2024.04.017" target="_blank" rel="noopener noreferrer" aria-label="DOI: Assessing the Clinical Utility of Published Prostate Cancer Polygenic Risk Scores in a Large Biobank Data Set">DOI</a>
<a href="https://pubmed.ncbi.nlm.nih.gov/38734542/" target="_blank" rel="noopener noreferrer" aria-label="PubMed: Assessing the Clinical Utility of Published Prostate Cancer Polygenic Risk Scores in a Large Biobank Data Set">PubMed</a>
</div>
</div>
</article>
<article class="publication-item" id="als-risk-prediction-2024">
<div class="publication-year"><span class="visually-hidden">Published </span>2024</div>
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<h3>Improving prediction models of amyotrophic lateral sclerosis (ALS) using polygenic, pre-existing conditions, and survey-based risk scores in the UK Biobank</h3>
<p class="publication-venue">Journal of Neurology</p>
<p class="publication-significance"><strong>Why it matters:</strong> Genetics, diagnoses, and survey measures did not contribute equally. In UK Biobank, polygenic scores for amyotrophic lateral sclerosis (ALS) offered modest discrimination. Adding diagnoses recorded before onset improved discrimination, while adding the exposure score did not. In this analysis, combining more types of data did not necessarily improve prediction.</p>
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<a href="https://doi.org/10.1007/s00415-024-12644-2" target="_blank" rel="noopener noreferrer" aria-label="DOI: Improving prediction models of amyotrophic lateral sclerosis (ALS) using polygenic, pre-existing conditions, and survey-based risk scores in the UK Biobank">DOI</a>
<a href="https://pubmed.ncbi.nlm.nih.gov/39249108/" target="_blank" rel="noopener noreferrer" aria-label="PubMed: Improving prediction models of amyotrophic lateral sclerosis (ALS) using polygenic, pre-existing conditions, and survey-based risk scores in the UK Biobank">PubMed</a>
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</article>
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</section>
<section class="home-section" aria-labelledby="people-title">
<div class="section-heading">
<div><p class="eyebrow">People</p><h2 id="people-title">A team working across disciplines</h2><p>Our researchers at Michigan Medicine and the School of Public Health bring experience in statistical genetics, clinical research, and research software development.</p></div>
<a class="text-link" href="/people/">Lab members and alumni →</a>
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<div class="people-strip">
<div class="person-summary"><strong>Lars Fritsche, PhD</strong><span>Lab Head</span></div><div class="person-summary"><strong>Ryan Welch, PhD</strong><span>Application Programmer/Analyst Lead</span></div><div class="person-summary"><strong>Sarah Fazal, PhD</strong><span>Postdoctoral Research Fellow</span></div><div class="person-summary"><strong>Shivalika Pathania, PhD</strong><span>Postdoctoral Research Fellow</span></div><div class="person-summary"><strong>Tai Yang, MS</strong><span>Graduate Student Research Assistant (GSRA) and PhD Candidate</span></div>
</div>
</section>
<section class="home-section" aria-labelledby="updates-title">
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<div><p class="eyebrow">Latest</p><h2 id="updates-title">Research stories, talks, and project news</h2></div>
<a class="text-link" href="/news/">All news →</a>
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<article class="news-card news-card--illustrated">
<p class="card-kicker"><time datetime="2026-08-03T00:00:00-04:00">August 2026</time> · Conference presentation</p>
<h3><a href="/news/psyprsweb-jsm-2026/">PsyPRSweb at JSM 2026</a></h3>
<p class="card-summary">PsyPRSweb benchmarks polygenic scores for mental health phenotypes across ancestry groups and biobanks.</p>
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<img src="/assets/images/news/psyprsweb-jsm-2026.svg" alt="Polygenic score sheets connected to equally sized biobank symbols for evaluation." width="480" height="280" loading="lazy" />
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<img src="/assets/images/news/psyprsweb-jsm-2026.svg#dark" alt="Polygenic score sheets connected to equally sized biobank symbols for evaluation." width="480" height="280" loading="lazy" />
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</article>
<article class="news-card news-card--illustrated">
<p class="card-kicker"><time datetime="2026-06-08T00:00:00-04:00">June 2026</time> · Funding</p>
<h3><a href="/news/postoperative-depression-project-2026/">Studying depressive symptoms after surgery</a></h3>
<p class="card-summary">A two-year project aims to identify patients who may need additional support for depressive symptoms after surgery.</p>
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<img src="/assets/images/news/postoperative-depression-project-2026.svg" alt="Hospital care followed by a six-month calendar illustrates studying depressive symptoms after surgery." width="480" height="280" loading="lazy" />
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<img src="/assets/images/news/postoperative-depression-project-2026.svg#dark" alt="Hospital care followed by a six-month calendar illustrates studying depressive symptoms after surgery." width="480" height="280" loading="lazy" />
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</article>
<article class="news-card news-card--illustrated">
<p class="card-kicker"><time datetime="2026-06-08T00:00:00-04:00">June 2026</time> · Research story</p>
<h3><a href="/news/compass-mental-health-care-2026/">U-M researchers aim to shorten the path to effective mental health care</a></h3>
<p class="card-summary">COMPASS participants contribute repeated reports, genetic samples, and health record data to study why mental health treatment responses differ.</p>
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<img src="/assets/images/news/compass-mental-health-care-2026.svg" alt="Participant reports, genetic samples, and health records contribute to COMPASS." width="480" height="280" loading="lazy" />
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<img src="/assets/images/news/compass-mental-health-care-2026.svg#dark" alt="Participant reports, genetic samples, and health records contribute to COMPASS." width="480" height="280" loading="lazy" />
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</article>
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<div><p class="eyebrow">Collaborate</p><h2 id="collaborate-title">Want to test a finding in another dataset or population?</h2><p>We collaborate on studies involving external validation, genomic data, longitudinal health records, and multimodal prediction.</p></div>
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<h2>Affiliations</h2>
<p>Michigan Medicine<br>Department of Anesthesiology<br>Department of Biostatistics</p>
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<h2>Connect</h2>
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<li><a href="https://medschool.umich.edu/profile/4980/lars-fritsche">Lars Fritsche’s U-M profile</a></li>
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