Predicting human height by Victorian and genomic methods.
In the Victorian era, Sir Francis Galton showed that 'when dealing with the transmission of stature from parents to children, the average height of the two parents, ... is all we need care to know about them' (1886). One hundred and twenty-two years after Galton's work was published, 54 loci showing strong statistical evidence for association to human height were described, providing us with potential genomic means of human height prediction. In a population-based study of 5748 people, we find that a 54-loci genomic profile explained 4-6% of the sex- and age-adjusted height variance, and had limited ability to discriminate tall/short people, as characterized by the area under the receiver-operating characteristic curve (AUC). In a family-based study of 550 people, with both parents having height measurements, we find that the Galtonian mid-parental prediction method explained 40% of the sex- and age-adjusted height variance, and showed high discriminative accuracy. We have also explored how much variance a genomic profile should explain to reach certain AUC values. For highly heritable traits such as height, we conclude that in applications in which parental phenotypic information is available (eg, medicine), the Victorian Galton's method will long stay unsurpassed, in terms of both discriminative accuracy and costs. For less heritable traits, and in situations in which parental information is not available (eg, forensics), genomic methods may provide an alternative, given that the variants determining an essential proportion of the trait's variation can be identified.
Aulchenko
Yurii S
YS
Department of Epidemiology and Biostatistics and Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands. i.aoultchenko@erasmusmc.nl
Struchalin
Maksim V
MV
Belonogova
Nadezhda M
NM
Axenovich
Tatiana I
TI
Weedon
Michael N
MN
Hofman
Albert
A
Uitterlinden
Andre G
AG
Kayser
Manfred
M
Oostra
Ben A
BA
van Duijn
Cornelia M
CM
Janssens
A Cecile J W
AC
Borodin
Pavel M
PM
D000704:Analysis of Variance; D001827:Body Height / Q000235:genetics*; D003198:Computer Simulation; D005544:Forecasting; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods*; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns / Q000502:physiology*; D008957:Models, Genetic; D012680:Sensitivity and Specificity