Dataset Information

Polygenic risk scores and the need for pharmacotherapy in neonatal abstinence syndrome.

ABSTRACT:

Background

The aim of this study was to identify genetic variants associated with NAS through a genome-wide association study (GWAS) and estimate a Polygenic Risk Score (PRS) model for NAS.

Methods

A prospective case-control study included 476 in utero opioid-exposed term neonates. A GWAS of 1000 genomes-imputed genotypes was performed to identify variants associated with need for pharmacotherapy for NAS. PRS models for estimating genetic predisposition were generated via a nested cross-validation approach using 382 neonates of European ancestry. PRS predictive ability, discrimination, and calibration were assessed.

Results

Cross-ancestry GWAS identified one intergenic locus on chromosome 7 downstream of SNX13 exhibiting genome-wide association with need for pharmacotherapy. PRS models derived from the GWAS for a subset of the European ancestry neonates reliably discriminated between need for pharmacotherapy using cis variant effect sizes within validation sets of European and African American ancestry neonates. PRS were less effective when applying variant effect sizes across datasets and in calibration analyses.

Conclusions

GWAS has the potential to identify genetic loci associated with need for pharmacotherapy for NAS and enable development of clinically predictive PRS models. Larger GWAS with additional ancestries are needed to confirm the observed SNX13 association and the accuracy of PRS in NAS risk prediction models.

Impact

Genetic associations appear to be important in neonatal abstinence syndrome. This is the first genome-wide association in neonates with neonatal abstinence syndrome. Polygenic risk scores can be developed examining single-nucleotide polymorphisms across the entire genome. Polygenic risk scores were higher in neonates receiving pharmacotherapy for treatment of their neonatal abstinence syndrome. Future studies with larger cohorts are needed to better delineate these genetic associations.

SUBMITTER: Bibi S

PROVIDER: S-EPMC9931940 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Polygenic risk scores and the need for pharmacotherapy in neonatal abstinence syndrome.

Bibi Shawana S Gaddis Nathan N Johnson Eric O EO Lester Barry M BM Kraft Walter W Singh Rachana R Terrin Norma N Adeniyi-Jones Susan S Davis Jonathan M JM

Pediatric research 20220816 5

<h4>Background</h4>The aim of this study was to identify genetic variants associated with NAS through a genome-wide association study (GWAS) and estimate a Polygenic Risk Score (PRS) model for NAS.<h4>Methods</h4>A prospective case-control study included 476 in utero opioid-exposed term neonates. A GWAS of 1000 genomes-imputed genotypes was performed to identify variants associated with need for pharmacotherapy for NAS. PRS models for estimating genetic predisposition were generated via a nested ...[more]

PMID: 35974158

Similar Datasets

Project description:Importance:Observer-rated scales, such as the Finnegan Neonatal Abstinence Scoring Tool (FNAST), are used to quantify the severity of neonatal abstinence syndrome (NAS) and guide pharmacologic therapy. The FNAST, a comprehensive 21-item assessment tool, was developed for research and subsequently integrated into clinical practice; a simpler tool, designed to account for clinically meaningful outcomes, is urgently needed to standardize assessment. Objectives:To identify FNAST items independently associated with the decision to use pharmacologic therapy and to simplify the FNAST while minimizing loss of information for the treatment decision. Design, Setting, and Participants:This multisite cohort study included 424 neonates with opioid exposure who had a gestational age of at least 36 weeks with follow-up from birth to hospital discharge in the derivation cohort and 109 neonates with opioid exposure from the Maternal Opioid Treatment: Human Experimental Research Study in the validation cohort. Neonates in the derivation cohort were included in a medical record review at the Universities of Louisville and Kentucky or in a randomized clinical trial and observational study conducted at Tufts University (2014-2018); the Maternal Opioid Treatment: Human Experimental Research was conducted from 2005 to 2008. Data analysis was conducted from May 2017 to August 2019. Exposures:Prenatal opioid exposure. Main Outcomes and Measures:All FNAST items were dichotomized as present or not present, and logistic regression was used to identify binary items independently associated with pharmacologic treatment. The final model was validated with an independent cohort of neonates with opioid exposure. Results:Among 424 neonates (gestational age, ≥36 weeks; 217 [51%] female infants), convulsions were not observed, and high-pitched cry and hyperactive Moro reflex had extremely different frequencies across cohorts. Therefore, these 3 FNAST items were removed from further analysis. The 2 tremor items were combined, and 8 of the remaining 17 items were independently associated with pharmacologic treatment, with an area under the curve of 0.86 (95% CI, 0.82-0.89) compared with 0.90 (95% CI, 0.87-0.94) for the 21-item FNAST. External validation of the 8 items resulted in an area under the curve of 0.86 (95% CI, 0.79-0.93). Thresholds of 4 and 5 on the simplified scale yielded the closest agreement with FNAST thresholds of 8 and 12 (weighted κ = 0.55; 95% CI, 0.48-0.61). Conclusions and Relevance:The findings of this study suggest that 8 signs of NAS may be sufficient to assess whether a neonate meets criteria for pharmacologic therapy. A focus on these signs could simplify the FNAST tool and may enhance its clinical utility.

Dataset Information

Polygenic risk scores and the need for pharmacotherapy in neonatal abstinence syndrome.

Background

Methods

Results

Conclusions

Impact

Publications

Polygenic risk scores and the need for pharmacotherapy in neonatal abstinence syndrome.

Similar Datasets

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