# Whole genome sequencing analysis of nonsyndromic craniosynostosis

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $159,583

## Abstract

PI: Simeon Boyd. MD
Project Abstract
Craniosynostosis (CS) is a major structural birth defect characterized by the premature fusion of one or more
cranial sutures that affects about 1 in 2,500 live births. Most CS cases present as nonsyndromic (NCS), an
isolated birth defect classified according to the suture(s) involved. NCS is considered a heterogeneous
multifactorial disease and primary prevention strategies for NCS are limited. The etiology of NCS is largely
unknown; however, findings generated by genomic technologies have begun to narrow this knowledge gap.
Using the specimen resources of our International Craniosynostosis Consortium and the National Birth Defects
Prevention Study, we successfully conducted the first two genome-wide association studies (GWAS)s for sagittal
NCS (sNCS) and metopic NCS (mNCS), performed next generation sequencing (NGS) of candidate loci for
sNCS and mNCS, and completed whole exome sequencing (WES) of more than 240 case-parent trios, multiplex,
and/or multigenerational families with NCS. These efforts have allowed us to identify robust associations to loci
near BMP2, BBS9, and within BMP7, as well as rare variants in biologic plausible genes involved in skeletal
development. With the support of grant X01 HL140535-01 from the Gabriella Miller Kids First Pediatric Research
Program we have already completed the whole genome sequencing (WGS) of 321 case-parent trios and
multiplex families with various types of NCS. In addition, samples from 31 of those families are currently in
process of long-read WGS. We hypothesize that the analysis of WGS and its integration with our extant genomic
data will identify novel genetic factors beyond those identified with GWAS’s that contribute to the etiology of
NCS. In this application, we propose to elucidate the genetic factors that contribute to NCS by implementing an
integrative genomic analysis of WGS in Aim 1. In Aim 2 we will comprehensively interrogate the genetic
architecture of NCS to identify all possible causal candidate genes and loci for NCS by harmonizing and
analyzing our existing genomic data accumulated from GWASs, WGS, WES, and NGS of affected families. In
Aim 3 we will perform initial characterization of likely causative variants and will prioritize them for future
molecular studies. Our extant genomic data represents one of the largest NCS data collections compiled and is
an unparalleled resource for studying the genetic etiology of NCS. Our approach will lay the foundation for
comprehensive integration of genomic data in order to identify candidate genes and loci and to pursue animal
models of NCS in the future. Given our past accomplishments, experienced interdisciplinary research team, and
substantial resources, we are well poised to achieve the aims of this proposal and provide critical insights into
the etiology of NCS.

## Key facts

- **NIH application ID:** 10490875
- **Project number:** 5R03DE031061-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Simeon A Boyadjiev Boyd
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $159,583
- **Award type:** 5
- **Project period:** 2021-09-17 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490875

## Citation

> US National Institutes of Health, RePORTER application 10490875, Whole genome sequencing analysis of nonsyndromic craniosynostosis (5R03DE031061-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10490875. Licensed CC0.

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