Accurate Genomic Prediction of Human Height

Genetics
Louis LelloStephen D H Hsu

Abstract

We construct genomic predictors for heritable but extremely complex human quantitative traits (height, heel bone density, and educational attainment) using modern methods in high dimensional statistics (i.e., machine learning). The constructed predictors explain, respectively, ∼40, 20, and 9% of total variance for the three traits, in data not used for training. For example, predicted heights correlate ∼0.65 with actual height; actual heights of most individuals in validation samples are within a few centimeters of the prediction. The proportion of variance explained for height is comparable to the estimated common SNP heritability from genome-wide complex trait analysis (GCTA), and seems to be close to its asymptotic value (i.e., as sample size goes to infinity), suggesting that we have captured most of the heritability for SNPs. Thus, our results close the gap between prediction R-squared and common SNP heritability. The ∼20k activated SNPs in our height predictor reveal the genetic architecture of human height, at least for common variants. Our primary dataset is the UK Biobank cohort, comprised of almost 500k individual genotypes with multiple phenotypes. We also use other datasets and SNPs found in earlier genome-wide asso...Continue Reading

References

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Citations

May 2, 2019·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Neta GevaGilad Twig
May 3, 2019·Genetic Epidemiology·Elizabeth A Thompson
Feb 28, 2019·Genetics·Florian PrivéMichael G B Blum
Oct 18, 2019·Journal of Personality Disorders·Susan C South
Oct 28, 2019·G3 : Genes - Genomes - Genetics·Zhijun DaiWen Huang
Mar 22, 2020·Genetics·Scott A FunkhouserGustavo de Los Campos
Dec 12, 2018·Nature Reviews. Cardiology·Maximillian A Rogers, Elena Aikawa
Nov 11, 2019·Nature Communications·Luke R Lloyd-JonesPeter M Visscher
Nov 21, 2019·Genome Medicine·Raquel Dias, Ali Torkamani
Jul 23, 2020·Scientific Reports·Soke Yuen YongStephen D H Hsu
Jul 1, 2020·Statistical Methods in Medical Research·Frank Dudbridge
Apr 17, 2020·International Journal of Molecular Sciences·Andrea P CabreraArup Das
Aug 9, 2020·Scientific Reports·Louis LelloStephen D H Hsu
Jul 28, 2020·Nature Protocols·Shing Wan ChoiPaul F O'Reilly
Jul 10, 2019·Annual Review of Genomics and Human Genetics·Guy Sella, Nicholas H Barton
Oct 28, 2020·G3 : Genes - Genomes - Genetics·Fabio MorganteTrudy F C Mackay
Dec 15, 2020·American Journal of Human Biology : the Official Journal of the Human Biology Council·Daniel J Hruschka
Feb 2, 2021·Frontiers in Genetics·Maria Lie SelleGregor Gorjanc
Aug 16, 2019·Emerging Topics in Life Sciences·Sara HäggAlan A Cohen
Nov 21, 2020·The Plant Genome·Filipe C AlvesGustavo de Los Campos
Feb 28, 2021·European Journal of Human Genetics : EJHG·Richard J ReynoldsAna I Vazquez
Mar 31, 2021·British Journal of Haematology·Janine CollinsDragana Vuckovic
May 7, 2021·Genetics·Scott A FunkhouserGustavo de Los Campos
May 10, 2021·BMC Pediatrics·Avivit BrenerYael Lebenthal
May 13, 2021·Wellcome Open Research·Robert F Hillary, Riccardo E Marioni
Apr 1, 2021·The Journal of Clinical Endocrinology and Metabolism·Tianyuan LuJ Brent Richards
Feb 20, 2021·The Journal of Clinical Endocrinology and Metabolism·Michael ShmoishZe'ev Hochberg
Jul 15, 2021·International Journal of Legal Medicine·Magdalena Kukla-BartoszekWojciech Branicki

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