Research program

Pain Genetics and Phenotyping

How do genetic differences and measurement choices affect the results of pain studies?

We study the genetics of pain and define pain phenotypes using clinical records, imaging, and patient-reported data.

Why pain phenotyping matters

Pain is not a single trait. Its location, duration, severity, and course can differ substantially between people, and each data source captures only part of that experience. Careful phenotyping is therefore essential for finding and interpreting genetic contributions to pain.

How we study pain genetics and phenotypes

Define pain phenotypes carefully

We distinguish pain by features such as location, duration, severity, co-occurrence, and trajectory instead of treating it as one outcome.

Study the genetic architecture of pain

We use statistical genetics to estimate heritability and identify genetic variation associated with well-defined pain phenotypes.

Use complementary measures

Together, clinical records, imaging, and patient reports can define pain more precisely than any one source alone.

Compare and replicate findings

We test whether other cohorts, data sources, and populations produce similar results.

Projects and papers

Current collaborations include the endometriosis-associated pelvic pain project led by Sawsan As-Sanie and Andrew Schrepf, and the U-M HEAL PAIN Cohort Program led by Daniel Clauw, Kelley McLain Kidwell, and Jenna Wiens. The selected papers show why clear phenotype definitions matter when interpreting genetic results across chronic pain conditions.

Current work

Projects and collaborations

Pain and women's health

Active

Endometriosis-associated pelvic pain mechanisms

The project examines whether differences in brain structure and connectivity are related to pelvic pain that persists after endometriosis treatment.

Sawsan As-Sanie and Andrew Schrepf are the principal investigators.

Eunice Kennedy Shriver National Institute of Child Health and Human Development
R01 · R01HD117775 · 2025-present

Pain research training

Active

U-M HEAL PAIN Cohort Program

The U-M HEAL PAIN T90/R90 Cohort Program provides research training and mentoring for early-career chronic pain researchers.

Daniel Clauw, Kelley McLain Kidwell, and Jenna Wiens are the principal investigators.

NIH HEAL Initiative
T90/R90 · T90DE034663 / R90DE034663 · 2024-2029 for T90/R90

Publications

Selected papers

All publications →
2022

Genome-wide analysis identifies impaired axonogenesis in chronic overlapping pain conditions

Brain

Why it matters: Combining all chronic pain locations into one phenotype can obscure important biological differences. Genetic contributions were stronger for multisite than single-site pain; nine of 23 multisite loci replicated in HUNT, while functional genomics and brain imaging pointed toward axonogenesis and corticolimbic circuitry. The results also depend on how researchers define the pain phenotype.

2021

Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain

Ann Rheum Dis

2020

Heritability of the Fibromyalgia Phenotype Varies by Age

Arthritis Rheumatol

2022

Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia

Pain

Why it matters: No single assay is likely to capture all of the biology underlying fibromyalgia. Across patient cohorts, flow cytometry, blood transcriptomics, genetic analyses, and skin biopsy each pointed toward altered natural killer (NK) cell biology, including NK cells near peripheral nerves. Together, the findings support further study of a possible role for NK cells, but they do not show that NK cells cause fibromyalgia.