#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
preLekára.sk / Odborné časopisy / PLOS Genetics / 2015 - 5

Genomic Heritability: What Is It?

English version České info

Whole-genome regression (WGR) methods are being increasingly used for inferring the proportion of variance that can be explained by a linear regression on a massive number of markers, called ‘genomic heritability.’ However, the statistical assumptions involved in WGRs are somewhat at odds with important quantitative genetics concepts. We argue and show that the parameters of the statistical model used for data analysis typically bear a tenuous relationship with the quantitative genetic parameters of interest. We also study, using simulations, the extent of bias of likelihood-based estimates. We conclude that under certain circumstances estimates can have a sizable finite-sample bias; therefore, caution needs to be exercised when interpreting parameter estimates derived from WGR models.

Vyšlo v časopise: Genomic Heritability: What Is It?. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005048
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005048

Souhrn

Whole-genome regression (WGR) methods are being increasingly used for inferring the proportion of variance that can be explained by a linear regression on a massive number of markers, called ‘genomic heritability.’ However, the statistical assumptions involved in WGRs are somewhat at odds with important quantitative genetics concepts. We argue and show that the parameters of the statistical model used for data analysis typically bear a tenuous relationship with the quantitative genetic parameters of interest. We also study, using simulations, the extent of bias of likelihood-based estimates. We conclude that under certain circumstances estimates can have a sizable finite-sample bias; therefore, caution needs to be exercised when interpreting parameter estimates derived from WGR models.

Zdroje

1. Meuwissen TH, Hayes BJ, Goddard ME (2001) Prediction of total genetic value using genome-wide dense marker maps. Genetics 157 : 1819–1829. 11290733

2. VanRaden P (2008) Efficient methods to compute genomic predictions. J Dairy Sci 91 : 4414–4423. doi: 10.3168/jds.2007-0980 18946147

3. Crossa J, de los Campos G, Perez P, Gianola D, Burgueño J, et al. (2010) Prediction of genetic values of quantitative traits in plant breeding using pedigree and molecular markers. Genetics 186 : 713–724. doi: 10.1534/genetics.110.118521 20813882

4. Yang J, Benyamin B, McEvoy BP, Gordon S, Henders AK, et al. (2010) Common SNPs explain a large proportion of the heritability for human height. Nat Genet 42 : 565–569. doi: 10.1038/ng.608 20562875

5. Speed D, Hemani G, Johnson MR, Balding DJ (2012) Improved heritability estimation from genome-wide SNPs. Am J Hum Genet 91 : 1011–1021. doi: 10.1016/j.ajhg.2012.10.010 23217325

6. de los Campos G, Vazquez AI, Fernando R, Klimentidis YC, Sorensen D (2013) Prediction of Complex Human Traits Using the Genomic Best Linear Unbiased Predictor. PLoS Genet 9: e1003608. doi: 10.1371/journal.pgen.1003608 23874214

7. de los Campos G, Sorensen DA (2013) A commentary on Pitfalls of predicting complex traits from SNPs. Nat Rev Genet 14 : 894–894. doi: 10.1038/nrg3457-c2 24240515

8. Henderson CR (1950) Estimation of genetic parameters. Ann Math Stat 21 : 309–310.

9. Thompson EA (1975) The estimation of pairwise relationships. Ann Hum Genet 39 : 173–188. 1052764

10. Ritland K (1996) A marker-based method for inferences about quantitative inheritance in natural populations. Evolution: 1062–1073.

11. Lynch M, Ritland K (1999) Estimation of pairwise relatedness with molecular markers. Genetics 152 : 1753. 10430599

12. Morton NE, Yee S, Harris DE, Lew R (1971) Bioassay of kinship. Theor Popul Biol 2 : 507–524. 5162702

13. Thomas SC (2005) The estimation of genetic relationships using molecular markers and their efficiency in estimating heritability in natural populations. Philos Trans R Soc B Biol Sci 360 : 1457–1467.

14. Zaitlen N, Kraft P (2012) Heritability in the genome-wide association era. Hum Genet 131 : 1655–1664. doi: 10.1007/s00439-012-1199-6 22821350

15. Bulmer MG (1980) The Mathematical Theory of Quantitative Genetics. Oxford University Press. 262 p.

16. Falconer DS, Mackay TFC (1996) Introduction to Quantitative Genetics (4th Edition). 4 edition. Benjamin Cummings.

17. Lynch M, Walsh B (1998) Genetics and analysis of quantitative traits. Available: http://www.invemar.org.co/redcostera1/invemar/docs/RinconLiterario/2011/febrero/AG_8.pdf. Accessed 2 December 2013.

18. Hill WG, Robertson A (1966) The effect of linkage on limits to artificial selection. Genet Res 8 : 269–294. 5980116

19. Avery PJ, Hill WG (1977) Variability in genetic parameters among small populations. Genet Res 29 : 193–213. 892441

20. Gianola D, Hospital F, Verrier E (2013) Contribution of an additive locus to genetic variance when inheritance is multi-factorial with implications on interpretation of GWAS. Theor Appl Genet 126 : 1457–1472. doi: 10.1007/s00122-013-2064-2 23508282

21. Goddard M (2009) Genomic selection: prediction of accuracy and maximisation of long term response. Genetica 136 : 245–257. doi: 10.1007/s10709-008-9308-0 18704696

22. Gianola D, de los Campos G, Hill WG, Manfredi E, Fernando R (2009) Additive genetic variability and the Bayesian alphabet. Genetics 183 : 347–363. doi: 10.1534/genetics.109.103952 19620397

23. Gianola D (2013) Priors in whole-genome regression: the Bayesian alphabet returns. Genetics 194 : 573–596. doi: 10.1534/genetics.113.151753 23636739

24. Lehmann EL, Casella G (1998) Theory of point estimation. Springer.

25. Cornelis MC, Agrawal A, Cole JW, Hansel NN, Barnes KC, et al. (2010) The Gene, Environment Association Studies consortium (GENEVA): maximizing the knowledge obtained from GWAS by collaboration across studies of multiple conditions. Genet Epidemiol 34 : 364–372. doi: 10.1002/gepi.20492 20091798

26. Li CC, Horvitz DG (1953) Some methods of estimating the inbreeding coefficient. Am J Hum Genet 5 : 107. 13065259

27. Ritland K (2000) Marker-inferred relatedness as a tool for detecting heritability in nature. Mol Ecol 9 : 1195–1204. 10972759

28. Toro M, Barragán C, Óvilo C, Rodrigañez J, Rodriguez C, et al. (2002) Estimation of coancestry in Iberian pigs using molecular markers. Conserv Genet 3 : 309–320.

29. Visscher PM, Hill WG, Wray NR (2008) Heritability in the genomics era—concepts and misconceptions. Nat Rev Genet 9 : 255–266. doi: 10.1038/nrg2322 18319743

30. Gianola D, Perez-Enciso M, Toro MA (2003) On marker-assisted prediction of genetic value: beyond the ridge. Genetics 163 : 347–365. 12586721

31. Yang W, Tempelman RJ (2012) A Bayesian Antedependence Model for Whole Genome Prediction. Genetics: 1491–1501. doi: 10.1534/genetics.111.131540 22135352

32. Hill WG, Weir BS (2011) Variation in actual relationship as a consequence of Mendelian sampling and linkage. Genet Res 93 : 47–64. doi: 10.1017/S0016672310000480 21226974

33. Goddard ME, Hayes BJ, Meuwissen THE (2011) Using the genomic relationship matrix to predict the accuracy of genomic selection. J Anim Breed Genet 128 : 409–421. doi: 10.1111/j.1439-0388.2011.00964.x 22059574

34. Jiang J., Li C., Debashis P., Yang C. and Zhao H (2014) High-dimensional Genome-wide Association Study and Misspecified Mixed Model Analysis. eprint arXiv:1404.2355.

35. Lee SH, Yang J, Chen G -⁠ B, Ripke S, Stahl EA, et al. (2013) Estimation of SNP heritability from dense genotype data. Am J Hum Genet 93 : 1151–1155. doi: 10.1016/j.ajhg.2013.10.015 24314550

36. Speed D, Hemani G, Johnson MR, Balding DJ (2013) Response to Lee et al.: SNP-Based Heritability Analysis with Dense Data. Am J Hum Genet 93 : 1155–1157. doi: 10.1016/j.ajhg.2013.10.016 24314551

37. Sorensen D, Fernando R, Gianola D (2001) Inferring the trajectory of genetic variance in the course of artificial selection. Genet Res 77 : 83–94. 11279833

Štítky
Genetika Reprodukčná medicína
Článek Triglyceride-Increasing Alleles Associated with Protection against Type-2 Diabetes
Článek Epistasis Is a Major Determinant of the Additive Genetic Variance in
Článek Genetic Regulation of Bone Metabolism in the Chicken: Similarities and Differences to Mammalian Systems
Článek Minor Type IV Collagen α5 Chain Promotes Cancer Progression through Discoidin Domain Receptor-1
Článek The Philosophical Approach: An Interview with Ford Doolittle
Článek Downregulation of the Host Gene by miR-92 Is Essential for Neuroblast Self-Renewal in
Článek A Unique Virulence Gene Occupies a Principal Position in Immune Evasion by the Malaria Parasite
Článek Y Fuse? Sex Chromosome Fusions in Fishes and Reptiles
Článek Regulation of Active DNA Demethylation by a Methyl-CpG-Binding Domain Protein in
Článek Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape
Článek Autoselection of Cytoplasmic Yeast Virus Like Elements Encoding Toxin/Antitoxin Systems Involves a Nuclear Barrier for Immunity Gene Expression
Článek Genetic Architecture of Abdominal Pigmentation in
Článek Whole Genome DNA Binding Analysis of the Bacterial Replication Initiator and Transcription Factor DnaA
Článek The Centrosomal Linker and Microtubules Provide Dual Levels of Spatial Coordination of Centrosomes
Článek Parp3 Negatively Regulates Immunoglobulin Class Switch Recombination
Článek Burden Analysis of Rare Microdeletions Suggests a Strong Impact of Neurodevelopmental Genes in Genetic Generalised Epilepsies
Článek Cell Cycle Control by the Master Regulator CtrA in
Článek Myopathic Lamin Mutations Cause Reductive Stress and Activate the Nrf2/Keap-1 Pathway
Článek Monoallelic Loss of the Imprinted Gene Promotes Tumor Formation in Irradiated Mice
Článek Phylum-Level Conservation of Regulatory Information in Nematodes despite Extensive Non-coding Sequence Divergence
Článek Clustering and Negative Feedback by Endocytosis in Planar Cell Polarity Signaling Is Modulated by Ubiquitinylation of Prickle
Článek Dissecting the Function and Assembly of Acentriolar Microtubule Organizing Centers in Cells In Vivo
Článek MicroRNA-Dependent Transcriptional Silencing of Transposable Elements in Drosophila Follicle Cells
Článek β-Catenin Signaling Biases Multipotent Lingual Epithelial Progenitors to Differentiate and Acquire Specific Taste Cell Fates
Článek A Simple Auxin Transcriptional Response System Regulates Multiple Morphogenetic Processes in the Liverwort
Článek Parallel Gene Expression Differences between Low and High Latitude Populations of and .
Článek The Nutrient-Responsive Hormone CCHamide-2 Controls Growth by Regulating Insulin-like Peptides in the Brain of
Článek Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci
Článek PARP2 Is the Predominant Poly(ADP-Ribose) Polymerase in Arabidopsis DNA Damage and Immune Responses
Článek Drosophila Spaghetti and Doubletime Link the Circadian Clock and Light to Caspases, Apoptosis and Tauopathy
Článek Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap
Článek Rescue of DNA-PK Signaling and T-Cell Differentiation by Targeted Genome Editing in a Deficient iPSC Disease Model
Článek Disruption of Transcriptional Coactivator Sub1 Leads to Genome-Wide Re-distribution of Clustered Mutations Induced by APOBEC in Active Yeast Genes
Článek Yeast Killer Elements Hold Their Hosts Hostage
Článek Keeping in Shape the Dogma of Mitochondrial DNA Maternal Inheritance
Článek Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans
Článek Trading Places—Switching Frataxin Function by a Single Amino Acid Substitution within the [Fe-S] Cluster Assembly Scaffold
Článek Natural Variation Identifies , a Universal Gene Required for Cell Proliferation and Growth at High Temperatures in
Článek Mutations in Gene Are Associated with Predisposition to Breast Cancer
Článek The Whole of a Scientific Career: An Interview with Oliver Smithies
Článek Cell Specific eQTL Analysis without Sorting Cells
Článek Cooperative Action of Cdk1/cyclin B and SIRT1 Is Required for Mitotic Repression of rRNA Synthesis
Článek Systemic Regulation of RAS/MAPK Signaling by the Serotonin Metabolite 5-HIAA
Článek Reprogramming LCLs to iPSCs Results in Recovery of Donor-Specific Gene Expression Signature
Článek The Developmental Intestinal Regulator ELT-2 Controls p38-Dependent Immune Responses in Adult .
Článek Genetic Mechanism of Human Neutrophil Antigen 2 Deficiency and Expression Variations
Článek Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathway to Regulate Lipid Metabolism in
Článek Early Lineage Priming by Trisomy of Leads to Myeloproliferation in a Down Syndrome Model
Článek Turning into a Frataxin-Dependent Organism
Článek Accounting for Experimental Noise Reveals That mRNA Levels, Amplified by Post-Transcriptional Processes, Largely Determine Steady-State Protein Levels in Yeast
Článek Biological Significance of Photoreceptor Photocycle Length: VIVID Photocycle Governs the Dynamic VIVID-White Collar Complex Pool Mediating Photo-adaptation and Response to Changes in Light Intensity
Článek CTXφ Replication Depends on the Histone-Like HU Protein and the UvrD Helicase
Článek Disruption of miR-29 Leads to Aberrant Differentiation of Smooth Muscle Cells Selectively Associated with Distal Lung Vasculature
Článek Notch Is Required in Adult Sensory Neurons for Morphological and Functional Plasticity of the Olfactory Circuit
Článek Post-transcriptional Regulation of Keratinocyte Progenitor Cell Expansion, Differentiation and Hair Follicle Regression by
Článek PERK Limits Lifespan by Promoting Intestinal Stem Cell Proliferation in Response to ER Stress
Článek Casein Kinase 1 and Phosphorylation of Cohesin Subunit Rec11 (SA3) Promote Meiotic Recombination through Linear Element Formation
Článek Fibroblast Growth Factor 9 Regulation by MicroRNAs Controls Lung Development and Links Loss to the Pathogenesis of Pleuropulmonary Blastoma
Článek Auxin-Mediated Transcriptional System with a Minimal Set of Components Is Critical for Morphogenesis through the Life Cycle in
Článek The Broad-Spectrum Antiviral Protein ZAP Restricts Human Retrotransposition
Článek The 4E-BP Caf20p Mediates Both eIF4E-Dependent and Independent Repression of Translation
Článek Turning into a Frataxin-Independent Organism
Článek Promotion of Bone Morphogenetic Protein Signaling by Tetraspanins and Glycosphingolipids
Článek Essential Role of the ESX-5 Secretion System in Outer Membrane Permeability of Pathogenic Mycobacteria
Článek The Zinc-Finger Antiviral Protein ZAP Inhibits LINE and Alu Retrotransposition
Článok vyšiel v časopise

PLOS Genetics

2015 Číslo 5
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

nový kurz
Autori: doc. MUDr. David Zemánek, Ph.D., MUDr. Anna Chaloupka, Ph.D.
Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#