Polygenic risk score rivals mid-parental height for predicting adult short stature

medwireNews: A polygenic risk score for height can predict a child’s adult height with similar accuracy to their mid-parental height, say researchers.

“Often in clinical settings, the height of only one parent is known”, observe J Brent Richards (Jewish General Hospital, Montréal, Québec, Canada) and study co-authors.

And “in many more cases” one or both of the supplied parental heights are inaccurate, they add.

Moreover, they say that “large discrepancies in parental heights render mid-parental height a less valid adult height predictor, particularly when some parents do not achieve their genetically determined height because of disease that is not inherited by the child.”

The team therefore constructed a polygenic risk score based on 33,938 single nucleotide polymorphisms that were associated with adult height in a genome-wide association study of 354,058 White British people from the UK Biobank.

Among 81,902 Biobank participants, this risk score accounted for 71.1% of the total variation in adult height, after accounting for variables including age and sex.

Likewise, it accounted for 71.0% of the total variation in the adult height of 941 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), similar to the 72.6% explained by mid-parental height.

In receiver operating characteristic (ROC) curve analysis, the polygenic risk score had high accuracy for distinguishing between ALSPAC children who attained a normal adult stature and those who had short stature. Specifically, the area under the ROC curve was 0.843 (where 1.0 is perfect accuracy), which compared well to the 0.879 for mid-parental height.

“Further, combining mid-parental height and the polygenic risk score provided better prediction accuracy than either metric alone”, write the researchers in The Journal of Clinical Endocrinology & Metabolism.

The polygenic risk score plus mid-parental height accounted for 78.5% of the variability in adult height among the ALSPAC participants, which was a significant improvement over use of either predictor alone, and the area under the ROC curve for distinguishing between future normal and short stature increased to 0.904.

Richards and team say that mid-parental height reflects environmental factors shared by the parents and child that could influence height, whereas the polygenic risk score provides a more refined estimate of genetic influences on height.

“Hence, the two predictors provide non-overlapping information”, they say.

Combining the two measures increased predictive accuracy for short stature even when only one parental height was available. Adding the polygenic risk score to parental height increased the area under the ROC curve from 0.812 to 0.896 for the mother’s height and from 0.825 to 0.882 for the father’s height.

“Since genome-wide genotyping has become more affordable […], is undertaken once in a lifetime, and could be used to predict several health outcomes, genetic prediction of adult height in children and adolescents could be widely and cost-effectively applied in research and clinical practice”, the researchers conclude.

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

J Clin Endocrinol Metab 2021; doi:10.1210/clinem/dgab215
Martin Savage
Programme Director

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