A Polygenic Risk Score to Predict Future Adult Short Stature Among Children

Tianyuan Lu, Vincenzo Forgetta, Haoyu Wu, John R B Perry, Ken K Ong, Celia M T Greenwood, Nicholas J Timpson, Despoina Manoousaki, J Brent Richards*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

1 Citation (Scopus)
15 Downloads (Pure)

Abstract

Context
Adult height is highly heritable, yet no genetic predictor has demonstrated clinical utility compared to mid-parental height.

Objective
To develop a polygenic risk score for adult height and evaluate its clinical utility.

Design
A polygenic risk score was constructed based on meta-analysis of genome-wide association studies and evaluated on the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.

Subjects
Participants included 442,599 genotyped White British individuals in the UK Biobank, and 941 genotyped child-parent trios of European ancestry in the ALSPAC cohort.

Interventions
None.

Main Outcome Measures
Standing height was measured using stadiometer; Standing height two standard deviations below the sex-specific population average was considered as short stature.

Results
Combined with sex, a polygenic risk score captured 71.1% of the total variance in adult height in the UK Biobank. In the ALSPAC cohort, the polygenic risk score was able to identify children who developed adulthood short stature with an area under the receiver operating characteristic curve (AUROC) of 0.84, which is close to that of mid-parental height. Combining this polygenic risk score with mid-parental height, or only one of the child’s parent’s height, could improve the AUROC to at most 0.90. The polygenic risk score could also substitute mid-parental height in age-specific Khamis-Roche height predictors and achieve an equally strong discriminative power in identifying children with a short stature in adulthood.

Conclusions
A polygenic risk score could be considered as an alternative or adjunct to mid-parental height to improve screening for children at risk of developing short stature in adulthood in European ancestry populations.
Original languageEnglish
Article numberdgab215
Pages (from-to)1918-1928
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume106
Issue number7
Early online date31 Mar 2021
DOIs
Publication statusPublished - 16 Jun 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

Keywords

  • polygenic risk score
  • adult height prediction
  • short stature
  • parental height
  • UK Biobank
  • ALSPAC

Fingerprint

Dive into the research topics of 'A Polygenic Risk Score to Predict Future Adult Short Stature Among Children'. Together they form a unique fingerprint.

Cite this