From Galton to GWAS: quantitative genetics of human height.

Height has been studied in human genetics since the late 1800s. We review what we have learned about the genetic architecture of this trait from the resemblance between relatives and from genetic marker data. All empirical evidence points towards height being highly polygenic, with many loci contributing to variation in the population and most effect sizes appear to be small. Nevertheless, combining new genetic and genomic technologies with phenotypic measures on height on large samples facilitates new answers to old questions, including the basis of assortative mating in humans, estimation of non-additive genetic variation and partitioning between-cohort phenotypic differences into genetic and non-genetic underlying causes.

[1]  FRANCIS GALTON Hereditary Stature , 1886, Nature.

[2]  Vibration of Telegraph-Wires , 1886, Nature.

[3]  F. Galton Regression Towards Mediocrity in Hereditary Stature. , 1886 .

[4]  K. Pearson,et al.  ON THE LAWS OF INHERITANCE IN MAN I. INHERITANCE OF PHYSICAL CHARACTERS , 1903 .

[5]  R. Fisher XV.—The Correlation between Relatives on the Supposition of Mendelian Inheritance. , 1919, Transactions of the Royal Society of Edinburgh.

[6]  Andrew Harris,et al.  Anthropology , 1907, Nature.

[7]  H. Grüneberg,et al.  Introduction to quantitative genetics , 1960 .

[8]  W. Kannel,et al.  Factors of risk in the development of coronary heart disease--six year follow-up experience. The Framingham Study. , 1961, Annals of internal medicine.

[9]  Morton Ne Analysis of family resemblance. I. Introduction. , 1974 .

[10]  N. Morton Analysis of family resemblance. I. Introduction. , 1974, American journal of human genetics.

[11]  W. Kannel,et al.  An investigation of coronary heart disease in families. The Framingham offspring study. , 1979, American journal of epidemiology.

[12]  L. Peltonen,et al.  Location on chromosome 15 of the gene defect causing Marfan syndrome. , 1990, The New England journal of medicine.

[13]  D. Goldgar Multipoint analysis of human quantitative genetic variation. , 1990, American journal of human genetics.

[14]  N L Segal,et al.  “Sources of Human Psychological Differences: The Minnesota Study of Twins Reared Apart” (1990), by , 2018 .

[15]  Anthropology. Why are pygmies small? , 1991, Nature.

[16]  M. Mattei,et al.  Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes , 1991, Nature.

[17]  J. Diamond Why are pygmies small? , 1991, Nature.

[18]  J. Gusella,et al.  The gene for achondroplasia maps to the telomeric region of chromosome 4p , 1994, Nature Genetics.

[19]  Xianjin Zhou,et al.  Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C , 1995, Nature.

[20]  R. Bailey,et al.  Allometry and adaptation of body proportions and stature in African pygmies. , 1996, American journal of physical anthropology.

[21]  N. Martin,et al.  Biological and cultural inheritance of stature and attitudes , 1999 .

[22]  C. R. Cloninger,et al.  Personality and psychopathology , 1999 .

[23]  D. Gunnell,et al.  Height, leg length, and cancer risk: a systematic review. , 2001, Epidemiologic reviews.

[24]  M. Goddard,et al.  Prediction of total genetic value using genome-wide dense marker maps. , 2001, Genetics.

[25]  S. Leal Genetics and Analysis of Quantitative Traits , 2001 .

[26]  E. Lander,et al.  Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height. , 2001, American journal of human genetics.

[27]  Jennifer R. Harris,et al.  Heritability of Adult Body Height: A Comparative Study of Twin Cohorts in Eight Countries , 2003, Twin Research.

[28]  T. Cole The secular trend in human physical growth: a biological view. , 2003, Economics and human biology.

[29]  J. Dekkers,et al.  Quantitative genetic variance associated with chromosomal markers in segregating populations , 1991, Theoretical and Applied Genetics.

[30]  P. Visscher,et al.  Detection of putative quantitative trait loci in line crosses under infinitesimal genetic models , 1996, Theoretical and Applied Genetics.

[31]  M. Olivier A haplotype map of the human genome , 2003, Nature.

[32]  M. Olivier A haplotype map of the human genome. , 2003, Nature.

[33]  Cynthia C Morton,et al.  Constitutional rearrangement of the architectural factor HMGA2: a novel human phenotype including overgrowth and lipomas. , 2005, American journal of human genetics.

[34]  Hui Shen,et al.  Genetic linkage of human height is confirmed to 9q22 and Xq24 , 2006, Human Genetics.

[35]  P. Visscher,et al.  Bias, precision and heritability of self-reported and clinically measured height in Australian twins , 2006, Human Genetics.

[36]  Manuel A. R. Ferreira,et al.  Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings , 2006, PLoS genetics.

[37]  Richa Saxena,et al.  A common variant of HMGA2 is associated with adult and childhood height in the general population , 2007, Nature Genetics.

[38]  W. G. Hill,et al.  Genome partitioning of genetic variation for height from 11,214 sibling pairs. , 2007, American journal of human genetics.

[39]  Qiong Yang,et al.  The Third Generation Cohort of the National Heart, Lung, and Blood Institute's Framingham Heart Study: design, recruitment, and initial examination. , 2007, American journal of epidemiology.

[40]  C. Quintana‐Domeque,et al.  The evolution of adult height in Europe: a brief note. , 2007, Economics and human biology.

[41]  M. Goddard Genomic selection: prediction of accuracy and maximisation of long term response , 2009, Genetica.

[42]  W. G. Hill,et al.  Data and Theory Point to Mainly Additive Genetic Variance for Complex Traits , 2008, PLoS genetics.

[43]  C. Gieger,et al.  Identification of ten loci associated with height highlights new biological pathways in human growth , 2008, Nature Genetics.

[44]  Ross J. Harris,et al.  Height and Prostate Cancer Risk: A Large Nested Case-Control Study (ProtecT) and Meta-analysis , 2008, Cancer Epidemiology Biomarkers & Prevention.

[45]  David M. Evans,et al.  Genome-wide association analysis identifies 20 loci that influence adult height , 2008, Nature Genetics.

[46]  T. Frayling,et al.  Reaching new heights: insights into the genetics of human stature. , 2008, Trends in Genetics.

[47]  Bjarni V. Halldórsson,et al.  Many sequence variants affecting diversity of adult human height , 2008, Nature Genetics.

[48]  W. G. Hill,et al.  Heritability in the genomics era — concepts and misconceptions , 2008, Nature Reviews Genetics.

[49]  Shah Ebrahim,et al.  Common variants in the GDF5-UQCC region are associated with variation in human height , 2008, Nature Genetics.

[50]  Peter M Visscher,et al.  Sizing up human height variation , 2008, Nature Genetics.

[51]  N. Siva 1000 Genomes project , 2008, Nature Biotechnology.

[52]  Judy H. Cho,et al.  Finding the missing heritability of complex diseases , 2009, Nature.

[53]  Taesung Park,et al.  A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits , 2009, Nature Genetics.

[54]  A. Hofman,et al.  Predicting human height by Victorian and genomic methods , 2009, European Journal of Human Genetics.

[55]  P. Visscher,et al.  Common polygenic variation contributes to risk of schizophrenia and bipolar disorder , 2009, Nature.

[56]  G. Perry,et al.  Evolution of the human pygmy phenotype. , 2009, Trends in ecology & evolution.

[57]  Peter M Visscher,et al.  Genetics of human height. , 2009, Economics and human biology.

[58]  Naomi R. Wray,et al.  Estimating Effects and Making Predictions from Genome-Wide Marker Data , 2010, 1010.4710.

[59]  G. Gibson Hints of hidden heritability in GWAS , 2010, Nature Genetics.

[60]  Y. Kamatani,et al.  A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci. , 2010, Human Molecular Genetics.

[61]  Nilanjan Chatterjee,et al.  Estimation of effect size distribution from genome-wide association studies and implications for future discoveries , 2010, Nature Genetics.

[62]  Ayellet V. Segrè,et al.  Hundreds of variants clustered in genomic loci and biological pathways affect human height , 2010, Nature.

[63]  P. Visscher,et al.  A Commentary on ‘Common SNPs Explain a Large Proportion of the Heritability for Human Height’ by Yang et al. (2010) , 2010, Twin Research and Human Genetics.

[64]  P. Visscher,et al.  Common SNPs explain a large proportion of heritability for human height , 2011 .

[65]  P. Visscher,et al.  The Genetic Interpretation of Area under the ROC Curve in Genomic Profiling , 2010, PLoS genetics.

[66]  L. Penrose,et al.  THE CORRELATION BETWEEN RELATIVES ON THE SUPPOSITION OF MENDELIAN INHERITANCE , 2022 .