Common DNA Variants Accurately Rank an Individual of Extreme Height

Abstract

Polygenic scores (or genetic risk scores) quantify the aggregate of small effects from many common genetic loci that have been associated with a trait through genome-wide association. Polygenic scores were first used successfully in schizophrenia and have since been applied to multiple phenotypes including multiple sclerosis, rheumatoid arthritis, and height. Because human height is an easily-measured and complex polygenic trait, polygenic height scores provide exciting insights into the predictability of aggregate common variant effect on the phenotype. Shawn Bradley is an extremely tall former professional basketball player from Brigham Young University and the National Basketball Association (NBA), measuring 2.29 meters (7'6^″, 99.99999th percentile for height) tall, with no known medical conditions. Here, we present a case where a rare combination of common SNPs in one individual results in an extremely high polygenic height score that is correlated with an extreme phenotype. While polygenic scores are not clinically significant in the average case, our findings suggest that for extreme phenotypes, polygenic scores may be more successful for the prediction of individuals.

Figure 1

Shawn Bradley is 2.29 m (7′ 6^″) tall with no known medical conditions. Mr. Bradley played basketball for Brigham Young University from 1990 to 1991. He played in the National Basketball Association from 1993–2005. Photo courtesy of BYU photography.

Figure 2

Height score distribution calculated using the 2910 SNPs. Mr. Bradley's height score (10.32, indicated by the arrow) ranked highest when compared to the 1020 individuals from ADNI and Cache County, while the next highest was 7.43. The mean height score within the ADNI and Cache County data was 0.98 with a standard deviation of 2.22, making Mr. Bradley's height score 4.2 standard deviations above the mean.

Figure 3

Correlation between height scores and self-reported height in the ADNI and Cache County individuals. We plotted height scores and self-reported heights (at age 18) for individuals in the ADNI and Cache County datasets and found poor correlation between the two. We also calculated the Pearson product moment correlation coefficient (correlation coefficient = 0.06, p = 0.25).