Comparison of methods that use whole genome data to estimate the heritability and genetic architecture of complex traits

Nature Genetics

Volumn 50, Issue 5, 2018, Pages 737-745

  Evans, Luke M ^a   Tahmasbi, Rasool ^a   Vrieze, Scott I ^b   Abecasis, Gonçalo R ^c   Das, Sayantan ^c   Gazal, Steven ^d,e   Bjelland, Douglas W ^a   De Candia, Teresa R ^a   Goddard, Michael E ^f,g   Neale, Benjamin M ^e   Yang, Jian ^h   Visscher, Peter M ^h   Keller, Matthew C ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

^c UNIVERSITY OF MICHIGAN   (United States)

^d HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^e BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^f UNIVERSITY OF MELBOURNE   (Australia)

^g AGRICULTURE VICTORIA RESEARCH   (Australia)

^h UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; BIOBANK; CASE CONTROL STUDY; CONFOUNDING VARIABLE; CONTROLLED STUDY; EFFECT SIZE; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENE STRUCTURE; GENETIC ANALYSIS; GENETIC ARCHITECTURE; GENETIC TRAIT; GENETIC VARIABILITY; GENOTYPE; HERITABILITY; HUMAN; INTERMETHOD COMPARISON; PHENOTYPE; PRIORITY JOURNAL; SIMULATION; SINGLE NUCLEOTIDE POLYMORPHISM; UNITED KINGDOM; WHOLE GENOME SEQUENCING; BIOLOGICAL MODEL; GENETICS; GENOME; GENOME-WIDE ASSOCIATION STUDY; MULTIFACTORIAL INHERITANCE; PROCEDURES; QUANTITATIVE TRAIT;

GENE FREQUENCY; GENOME; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; LINKAGE DISEQUILIBRIUM; MODELS, GENETIC; MULTIFACTORIAL INHERITANCE; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT, HERITABLE;

EID: 85046033174     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/s41588-018-0108-x     Document Type: Article

References (38)

1. Tenesa, A. & Haley, C. S. The heritability of human disease: estimation, uses and abuses. Nat. Rev. Genet. 14, 139-149 (2013).
2. Visscher, P. M., Hill, W. G. & Wray, N. R. Heritability in the genomics era-concepts and misconceptions. Nat. Rev. Genet. 9, 255-266 (2008).
3. Keller, M. C. & Coventry, W. L. Quantifying and addressing parameter indeterminacy in the classical twin design. Twin Res. Hum. Genet. 8, 201-213 (2005).
4. Eaves, L. J., Last, K. A., Young, P. A. & Martin, N. G. Model-fitting approaches to the analysis of human behaviour. Heredity (Edinb.) 41, 249-320 (1978).
5. Yang, J. et al. Common SNPs explain a large proportion of the heritability for human height. Nat. Genet. 42, 565-569 (2010).
6. Lee, S. H. et al. Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nat. Genet. 44, 247-250 (2012).
7. 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).
8. Hyde, C. L. et al. Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nat. Genet. 48, 1031-1036 (2016).
9. Okbay, A. et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat. Genet. 48, 624-633 (2016).
10. Finucane, H. K. et al. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat. Genet. 47, 1228-1235 (2015).
11. Yang, J. et al. Genome partitioning of genetic variation for complex traits using common SNPs. Nat. Genet. 43, 519-525 (2011).
12. Loh, P.-R. et al. Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysis. Nat. Genet. 47, 1385-1392 (2015).
13. Gazal, S. et al. Linkage disequilibrium-dependent architecture of human complex traits shows action of negative selection. Nat. Genet. 49, 1421-1427 (2017).
14. Zeng, J. et al. Signatures of negative selection in the genetic architecture of human complex traits. Nat. Genet. https://doi.org/10.1038/s41588-018-0101-4 (2018).
15. Speed, D., Cai, N., Johnson, M. R., Nejentsev, S. & Balding, D. J. Reevaluation of SNP heritability in complex human traits. Nat. Genet. 49, 986-992 (2017).
16. Lee, S. H. et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat. Genet. 45, 984-994 (2013).
17. Gusev, A. et al. Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases. Am. J. Hum. Genet. 95, 535-552 (2014).
18. Mancuso, N. et al. The contribution of rare variation to prostate cancer heritability. Nat. Genet. 48, 30-35 (2016).
19. Bulik-Sullivan, B. K. et al. LD score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 47, 291-295 (2015).
20. 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).
21. McCarthy, S. et al. A reference panel of 64,976 haplotypes for genotype imputation. Nat. Genet. 48, 1279-1283 (2016).
22. Bycroft, C. et al. Genome-wide genetic data on ~ 500,000 UK Biobank participants. Preprint at bioRxiv https://doi.org/10.1101/166298 (2017).
23. Yang, J., Zeng, J., Goddard, M. E., Wray, N. R. & Visscher, P. M. Concepts, estimation and interpretation of SNP-based heritability. Nat. Genet. 49, 1304-1310 (2017).
24. Zaitlen, N. et al. Using extended genealogy to estimate components of heritability for 23 quantitative and dichotomous traits. PLoS Genet. 9, e1003520 (2013).
25. Lee, S. H. et al. Estimation of SNP heritability from dense genotype data. Am. J. Hum. Genet. 93, 1151-1155 (2013).
26. Sudlow, C. et al. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 12, e1001779 (2015).
27. Wood, A. R. et al. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat. Genet. 46, 1173-1186 (2014).
28. 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).
29. Browning, S. R. & Browning, B. L. Population structure can inflate SNP-based heritability estimates. Am. J. Hum. Genet. 89, 191-193 (2011). author reply 193-195.
30. Goddard, M. E., Lee, S. H., Yang, J., Wray, N. R. & Visscher, P. M. Response to Browning and Browning. Am. J. Hum. Genet. 89, 193-195 (2011).
31. 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).
32. Zhu, Z. et al. Dominance genetic variation contributes little to the missing heritability for human complex traits. Am. J. Hum. Genet. 96, 377-385 (2015).
33. Abraham, G. & Inouye, M. Fast principal component analysis of large-scale genome-wide data. PLoS One 9, e93766 (2014).
34. Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015).
35. R Core Team. R: a Language and Environment for Statistical Computing. (R Foundation for Statistical Computing, Vienna, Austria, 2015).
36. 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).
37. Xia, C. et al. Pedigree-and SNP-associated genetics and recent environment are the major contributors to anthropometric and cardiometabolic trait variation. PLoS Genet. 12, e1005804 (2016).
38. Zuk, O., Hechter, E., Sunyaev, S. R. & Lander, E. S. The mystery of missing heritability: Genetic interactions create phantom heritability. Proc. Natl Acad. Sci. USA 109, 1193-1198 (2012).