Accuracy of heritability estimations in presence of hidden population stratification

Scientific Reports

Volumn 6, Issue 1, 2016, Pages

  Dandine Roulland, Claire ^a   Bellenguez, Céline ^b   Debette, Stéphanie ^c,d,e   Amouyel, Philippe ^b   Génin, Emmanuelle ^f,g,h   Perdry, Hervé ^a  

^a CENTRE FOR RESEARCH IN EPIDEMIOLOGY AND POPULATION HEALTH   (France)

^b LILLE UNIVERSITY HOSPITAL   (France)

^c UNIVERSITÉ DE BORDEAUX   (France)

^d INSERM   (France)

^e BORDEAUX UNIVERSITY HOSPITAL   (France)

^f CNRS   (France)

^g UNIVERSITÉ DE BRETAGNE OCCIDENTALE   (France)

^h BREST UNIVERSITY HOSPITAL   (France)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MODEL; BODY HEIGHT; FEMALE; FRANCE; GENETICS; HUMAN; MALE; PHYLOGEOGRAPHY; PRINCIPAL COMPONENT ANALYSIS; QUANTITATIVE TRAIT LOCUS; STATISTICAL MODEL; WAIST HIP RATIO;

BODY HEIGHT; FEMALE; FRANCE; HUMANS; LIKELIHOOD FUNCTIONS; MALE; MODELS, GENETIC; PHYLOGEOGRAPHY; PRINCIPAL COMPONENT ANALYSIS; QUANTITATIVE TRAIT LOCI; WAIST-HIP RATIO;

EID: 85019231073     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep26471     Document Type: Article

References (60)

1. Galton, F. Hereditary genius (Macmillan and Company, 1869).
2. Fisher, R. The correlation between relatives on the supposition of mendelian inheritance. Trans. R. Soc. Edinb. Earth Sci. 52, 399–433 (1918).
3. Falconer, D. S. Introduction to quantitative genetics (Oliver & Boyd, 1960).
4. Kempthorne, O. & Osborne, R. H. The interpretation of twin data. Am. J. Hum. Genet. 13, 320 (1961).
5. Scarr, S. Environmental bias in twin studies. Eugenics Q. 15, 34–40 (1968).
6. Feero, W. G., Guttmacher, A. E. & Manolio, T. A. Genomewide association studies and assessment of the risk of disease. N. Engl. J. Med. 363, 166–176 (2010).
7. Donnelly, P. Progress and challenges in genome-wide association studies in humans. Nature 456, 728–731 (2008).
8. Maher, B. Personal genomes: The case of the missing heritability. Nature 456, 18–21 (2008).
9. Visscher, P. M., Hill, W. G. & Wray, N. R. Heritability in the genomics era—concepts and misconceptions. Nat. Rev. Genet. 9, 255–266 (2008).
10. Zuk, O., Hechter, E., Sunyaev, S. R. & Lander, E. S. The mystery of missing heritability: Genetic interactions create phantom heritability. Proc. Natl. Acad. Sci. 109, 1193–1198 (2012).
11. Manolio, T. A. et al. Finding the missing heritability of complex diseases. Nature 461, 747–753 (2009).
12. Gusev, A. et al. Quantifying missing heritability at known gwas loci. PLos Genet. 9, e1003993 (2013).
13. Lee, S. H., Wray, N. R., Goddard, M. E. & Visscher, P. M. Estimating missing heritability for disease from genome-wide association studies. Am. J. Hum. Genet. 88, 294–305 (2011).
14. Yang, J. et al. Common SNPs explain a large proportion of the heritability for human height. Nat. Genet. 42, 565–569 (2010).
15. Goddard, M., Lee, H., Yang, J., Wray, N. & Visscher, P. Response to browning and browning. Am. J. Hum. Genet. 89, 193–195 (2011).
16. Browning, S. R. & Browning, B. L. Population structure can inflate SNP-based heritability estimates. Am. J. Hum. Genet. 89, 191–193 (2011).
17. Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).
18. Zhang, Y. & Pan, W. Principal component regression and linear mixed model in association analysis of structured samples: competitors or complements? Genet. Epidemiol. 39, 149–155 (2015).
19. Janss, L., de Los Campos, G., Sheehan, N. & Sorensen, D. Inferences from genomic models in stratified populations. Genetics 192, 693–704 (2012).
20. Segura, V. et al. An efficient multi-locus mixed-model approach for genome-wide association studies in structured populations. Nat. Genet. 44, 825–830 (2012).
21. Price, A. L., Zaitlen, N. A., Reich, D. & Patterson, N. New approaches to population stratification in genome-wide association studies. Nat. Rev. Genet. 11, 459–463 (2010).
22. Group, C. S. et al. Vascular factors and risk of dementia: design of the three-city study and baseline characteristics of the study population. Neuroepidemiology 22, 316 (2003).
23. Novembre, J. et al. Genes mirror geography within Europe. Nature 456, 98–101 (2008).
24. Galton, F. Regression towards mediocrity in hereditary stature. The Journal of the Anthropological Institute of Great Britain and Ireland 15, 246–263 (1886).
25. Allen, H. L. et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467, 832–838 (2010).
26. Lanktree, M. B. et al. Meta-analysis of dense genecentric association studies reveals common and uncommon variants associated with height. Am. J. Hum. Genet. 88, 6–18 (2011).
27. van der Valk, R. J. et al. A novel common variant in DCST2 is associated with length in early life and height in adulthood. Hum. Mol. Genet. 24, 1155–1168 (2015).
28. Speliotes, E. K. et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat. Genet. 42, 937–948 (2010).
29. Thorleifsson, G. et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat. Genet. 41, 18–24 (2009).
30. Loos, R. J. Genetic determinants of common obesity and their value in prediction. Best Pract. Res. Clin. Endocrinol. Metab. 26, 211–226 (2012).
31. Heid, I. M. et al. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat. Genet. 42, 949–960 (2010).
32. Lindgren, C. M. et al. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLos Genet. 5, e1000508 (2009).
33. Yoneyama, S. et al. Gene-centric meta-analyses for central adiposity traits in up to 57,412 individuals of european descent confirm known loci and reveal several novel associations. Hum. Mol. Genet. 23, 2498–2510 (2014).
34. Stram, D. O. & Lee, J. W. Variance components testing in the longitudinal mixed effects model. Biometrics 1171–1177 (1994).
35. Yang, J. et al. Genome partitioning of genetic variation for complex traits using common SNPs. Nat. Genet. 43, 519–525 (2011).
36. Kumar, S. K., Feldman, M. W., Rehkopf, D. H. & Tuljapurkar, S. Limitations of GCTA as a solution to the missing heritability problem. Proc. Natl. Acad. Sci. 113, E61–E70 (2016).
37. Yang, J., Lee, S. H., Wray, N. R., Goddard, M. E. & Visscher, P. M. Commentary on “Limitations of GCTA as a solution to the missing heritability problem”. bioRxiv (Date of access: 04/04/2016) URL http://biorxiv.org/content/early/2016/01/20/036574 (2016).
38. Génin, E. & Clerget-Darpoux, F. The missing heritability paradigm: A dramatic resurgence of the GIGO Syndrome in genetics. Hum. Hered. 79, 10–13 (2015).
39. Lee, S. H. & Van Der Werf, J. H. An efficient variance component approach implementing an average information REML suitable for combined LD and linkage mapping with a general complex pedigree. Genet. Sel. Evol. 38, 1–19 (2006).
40. Liu, D., Ghosh, D. & Lin, X. Estimation and testing for the effect of a genetic pathway on a disease outcome using logistic kernel machine regression via logistic mixed models. BMC Bioinformatics 9, 292 (2008).
41. Gilmour, A. R., Thompson, R. & Cullis, B. R. Average information REML: an efficient algorithm for variance parameter estimation in linear mixed models. Biometrics 1440–1450 (1995).
42. Lippert, C. et al. FaST linear mixed models for genome-wide association studies. Nat. Methods 8, 833–835 (2011).
43. Perdry, H. & Dandine-Roulland, C. Package R ‘gaston’, [version 1.4]. URL https://cran.r-project.org/web/packages/gaston/index.html (2015).
44. Yang, J., Lee, S. H., Goddard, M. E. & Visscher, P. M. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76–82 (2011).
45. Anderson, C. A. et al. Data quality control in genetic case-control association studies. Nat. Protoc. 5, 1564–1573 (2010).
46. Lambert, J.-C. et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat. Genet. 41, 1094–1099 (2009).
47. Purcell, S. et al. Plink: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).
48. Price, A. L. et al. Long-range LD can confound genome scans in admixed populations. Am. J. Hum. Genet. 83, 132 (2008).
49. Visscher, P. M. et al. Genome partitioning of genetic variation for height from 11,214 sibling pairs. Am. J. Hum. Genet. 81, 1104–1110 (2007).
50. Macgregor, S., Cornes, B. K., Martin, N. G. & Visscher, P. M. Bias, precision and heritability of self-reported and clinically measured height in Australian twins. Hum. Genet. 120, 571–580 (2006).
51. Silventoinen, K. et al. Heritability of adult body height: a comparative study of twin cohorts in eight countries. Twin Res. 6, 399–408 (2003).
52. Polderman, T. J. et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat. Genet. 47, 702–709 (2015).
53. Chen, X. et al. Dominant genetic variation and missing heritability for human complex traits: Insights from twin versus genome-wide common snp models. Am. J. Hum. Genet. 97, 708–714 (2015).
54. Visscher, P. M., Yang, J. & Goddard, M. E. A commentary on ‘common SNPs explain a large proportion of the heritability for human height’ by Yang et al. Twin Res. Hum. Genet. 13, 517–524 (2010).
55. Yang, J. et al. Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index. Nat. Genet. 47, 1114–1120 (2015).
56. Speed, D., Hemani, G., Johnson, M. R. & Balding, D. J. Improved heritability estimation from genome-wide SNPs. Am. J. Hum. Genet. 91, 1011–1021 (2012).
57. Yang, J. et al. Genome-wide genetic homogeneity between sexes and populations for human height and body mass index. Hum. Mol. Genet. ddv443 (2015).
58. Elks, C. E. et al. Variability in the heritability of body mass index: a systematic review and meta-regression. Front. Endocrinol. 3, 29 (2012).
59. Smit, D. J. et al. Heritability of head size in Dutch and Australian twin families at ages 0–50 years. Twin Res. Hum. Genet. 13, 370–380 (2010).
60. Ermakov, S., Kobyliansky, E. & Livshits, G. Quantitative genetic study of head size related phenotypes in ethnically homogeneous chuvasha pedigrees. Ann. Hum. Biol. 32, 585–598 (2005).