# Defining the multivariate genomic signature of pubertal markers and impact on lifespan psychopathology

> **NIH NIH K08** · UNIVERSITY OF COLORADO DENVER · 2023 · $169,679

## Abstract

PROJECT SUMMARY/ABSTRACT
Adolescent increases in psychopathology across multiple dimensions have a significant detrimental impact on
morbidity, mortality and well-being during this period of life, and set the stage for adult physical and mental health
difficulties. Prevalence rates of internalizing psychopathology, which is higher on average in females, and
externalizing psychopathology, higher in males, diverge during adolescence, and this trajectory continues on
subsequently over the lifespan, implicating sex-differentiated mechanisms. Consistent with this, a robust
literature supports individual differences in pubertal timing (e.g., onset) and pubertal tempo (e.g., rate of change)
as risk-factors for increased psychopathology. However, reliance on single sex-specific indicators, retrospective
reports, and cross-sectional data to measure this dynamic period of maturation have made identification of
mechanisms driving puberty and psychopathology links difficult. The current study aims to capitalize on
measured genomics approaches integrated with longitudinal data in both sexes to inform the genomic signal of
puberty across multiple physical and hormonal indicators, and examine genetic covariation between puberty and
psychopathology across the lifespan. The first aim will leverage the novel method of genomic structural equation
modeling (genomic SEM; training aim 1) to combine summary statistics from published genome-wise association
studies (GWAS) of pubertal timing (i.e., age of menarche, relative age of voice break, relative age of first facial
hair), pubertal growth spurt, pubertal maturation (i.e., Tanner staging), testosterone, estradiol, and sex hormone
binding globulin (SHBG) to identify latent pubertal genomic factors both specific to and unified across sex.
Polygenic scores (PGS; training aim 2) derived from the multivariate pubertal genomic factors will be validated
by out-of-sample prediction of longitudinally measured pubertal timing and tempo characterized by multiple
pubertal markers in the Adolescent Brain Cognitive Development (ABCD) Study. The second aim is to investigate
measured genetic covariance of multivariate pubertal genomic signal with lifespan sex-differentiated
psychopathology (training aim 3). This will be achieved through (a) examining correlations between the pubertal
genomic factor model and previously established factor models of the genetic architecture of adult psychiatric
traits using genomic SEM, and estimating pubertal PGS prediction of sex-specific lifetime psychiatric diagnoses
in the UKBiobank; and (b) probing sex-specific and sex-unified pubertal PGS effects on longitudinally modeled
adolescent symptoms of psychopathology in the ABCD Study, both directly and in conjunction with longitudinally
measured pubertal timing and tempo. This research will yield a comprehensive model of measured genomic
signal of puberty across multiple related phenotypes in both sexes, and provide improved tools for parsing
geneti...

## Key facts

- **NIH application ID:** 10641312
- **Project number:** 1K08MH132903-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Megan Wales Patterson
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $169,679
- **Award type:** 1
- **Project period:** 2023-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10641312

## Citation

> US National Institutes of Health, RePORTER application 10641312, Defining the multivariate genomic signature of pubertal markers and impact on lifespan psychopathology (1K08MH132903-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10641312. Licensed CC0.

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