publication . Article . 2015

Rare Variants in Transcript and Potential Regulatory Regions Explain a Small Percentage of the Missing Heritability of Complex Traits in Cattle.

Michael Goddard; Hans D Daetwyler; Oscar Gonzalez-Recio; Jennie Pryce; Ben Hayes;
Open Access
  • Published: 01 Dec 2015
  • Publisher: Public Library of Science (PLoS)
Abstract
The proportion of genetic variation in complex traits explained by rare variants is a key question for genomic prediction, and for identifying the basis of "missing heritability"--the proportion of additive genetic variation not captured by common variants on SNP arrays. Sequence variants in transcript and regulatory regions from 429 sequenced animals were used to impute high density SNP genotypes of 3311 Holstein sires to sequence. There were 675,062 common variants (MAF>0.05), 102,549 uncommon variants (0.01<MAF<0.05), and 83,856 rare variants (MAF<0.01). We describe a novel method for estimating the proportion of the rare variants that are sequencing errors u...
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51 references, page 1 of 4

1 Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al (2009) Finding the missing heritability. Nature 461: 747–753. 10.1038/nature08494 19812666 [OpenAIRE] [PubMed] [DOI]

2 Yang JB. Benyamin BP, McEvoy S, Gordon AK, Henders AK, Nyholt DR, et al (2010) Common SNPs explain a large proportion of the heritability for human height. Nat Genet 42: 565–569. 10.1038/ng.608 20562875 [OpenAIRE] [PubMed] [DOI]

3 Haile-Mariam M, Nieuwhorf GJ, Beard KT, Konstantinov KV, Hayes BJ (2013) Comparison of heritabilities of dairy traits in Australia Holstein Friesian cattle from genomic and pedigree data and implications for genomic evaluations. J Anim Breed Genet 130(1): 20–31. 10.1111/j.1439-0388.2013.01001.x 23317062 [OpenAIRE] [PubMed] [DOI]

4 Lee SH, DeCandia TR, Ripke S, Yang J. The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), The International Schizophrenia Consortium (ISC), et al (2012) Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nat. Genet. 44: 247–250. 10.1038/ng.1108 22344220 [OpenAIRE] [PubMed] [DOI]

5 Jensen J, Guosheng S, Madsen P (2012) Partitioning additive genetic variance into genomic and remaining polygenic components for complex traits in dairy cattle. Genet Sel Evol 13: 44.

6 Román-Ponce SI, SamoréAB, Dolezal MA, Bagnato A, Meuwissen THE (2014) Estimates of genetic heritability for complex traits in Brown Swiss cattle. Genet Sel Evol 46: 36 10.1186/1297-9686-46-36 24898214 [OpenAIRE] [PubMed] [DOI]

7 Gibson G (2012) Rare and common variants: twenty arguments. Nat Rev Genet 13: 135–145. 10.1038/nrg3118 22251874 [OpenAIRE] [PubMed] [DOI]

8 Zuk O, Schaffner SF, Samocha K, Do R, Hechter E, Kathiresan S, et al (2014) Searching for missing heritability: Designing rare variant association studies. PNAS 17: E455–E464. [OpenAIRE]

9 Cirulli ET, Goldstein DB (2010) Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet 11: 415 10.1038/nrg2779 20479773 [OpenAIRE] [PubMed] [DOI]

10 Gusev A, Hong Lee S, Trynka G, Finucane H, Vilhjálmsson BJ, Xu H, et al (2014) Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases. Amer. J. Human Genet 95: 535–552.25439723 [OpenAIRE] [PubMed]

11 Zuk O, Hechter E, Sunyaev SR, Lander ES (2012) The mystery of missing heritability: genetic interaction create phantom heritability. PNAS 109(4): 1193–1198. 10.1073/pnas.1119675109 22223662 [OpenAIRE] [PubMed] [DOI]

12 Daetwyler HD, Capitan A, Pausch H, Stothard P, van Binsbergen R, Brondum RF, et al 2014 Whole genome sequencing of 234 bulls facilitates mapping of monogenic and complex traits in cattle. Nat Genet 10.1038/ng.3034 [OpenAIRE] [DOI]

13 Meacham F, Boffelli D, Dhahbi J, Martin DI, Singer M, Pachter L (2011) Identification and correction of systematic error in high-throughput sequence data. BMC Bioinformatics 12: 451 10.1186/1471-2105-12-451 22099972 [OpenAIRE] [PubMed] [DOI]

14 Loman NJ, Misra RV, Dallman TJ, Constantinidou C, Gharbia SE, Wain J, et al (2012) Performance comparison of benchtop high-throughput sequencing platforms. Nat. Biotechnol 30 (5): 434–439. ISSN 1087-0156. 10.1038/nbt.2198 22522955 [OpenAIRE] [PubMed] [DOI]

15 Meuwissen THE, Hayes BJ, Goddard ME (2001) Prediction of total genetic value using genome-wide dense marker maps. Genet 157: 1819–1829.

51 references, page 1 of 4
Abstract
The proportion of genetic variation in complex traits explained by rare variants is a key question for genomic prediction, and for identifying the basis of "missing heritability"--the proportion of additive genetic variation not captured by common variants on SNP arrays. Sequence variants in transcript and regulatory regions from 429 sequenced animals were used to impute high density SNP genotypes of 3311 Holstein sires to sequence. There were 675,062 common variants (MAF>0.05), 102,549 uncommon variants (0.01<MAF<0.05), and 83,856 rare variants (MAF<0.01). We describe a novel method for estimating the proportion of the rare variants that are sequencing errors u...
Subjects
free text keywords: Medicine, R, Science, Q, Research Article
Related Organizations
Download fromView all 4 versions
PLoS ONE
Article . 2015
Provider: Crossref
PLoS ONE
Article
Provider: UnpayWall
PLoS ONE
Article . 2015
51 references, page 1 of 4

1 Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al (2009) Finding the missing heritability. Nature 461: 747–753. 10.1038/nature08494 19812666 [OpenAIRE] [PubMed] [DOI]

2 Yang JB. Benyamin BP, McEvoy S, Gordon AK, Henders AK, Nyholt DR, et al (2010) Common SNPs explain a large proportion of the heritability for human height. Nat Genet 42: 565–569. 10.1038/ng.608 20562875 [OpenAIRE] [PubMed] [DOI]

3 Haile-Mariam M, Nieuwhorf GJ, Beard KT, Konstantinov KV, Hayes BJ (2013) Comparison of heritabilities of dairy traits in Australia Holstein Friesian cattle from genomic and pedigree data and implications for genomic evaluations. J Anim Breed Genet 130(1): 20–31. 10.1111/j.1439-0388.2013.01001.x 23317062 [OpenAIRE] [PubMed] [DOI]

4 Lee SH, DeCandia TR, Ripke S, Yang J. The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), The International Schizophrenia Consortium (ISC), et al (2012) Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nat. Genet. 44: 247–250. 10.1038/ng.1108 22344220 [OpenAIRE] [PubMed] [DOI]

5 Jensen J, Guosheng S, Madsen P (2012) Partitioning additive genetic variance into genomic and remaining polygenic components for complex traits in dairy cattle. Genet Sel Evol 13: 44.

6 Román-Ponce SI, SamoréAB, Dolezal MA, Bagnato A, Meuwissen THE (2014) Estimates of genetic heritability for complex traits in Brown Swiss cattle. Genet Sel Evol 46: 36 10.1186/1297-9686-46-36 24898214 [OpenAIRE] [PubMed] [DOI]

7 Gibson G (2012) Rare and common variants: twenty arguments. Nat Rev Genet 13: 135–145. 10.1038/nrg3118 22251874 [OpenAIRE] [PubMed] [DOI]

8 Zuk O, Schaffner SF, Samocha K, Do R, Hechter E, Kathiresan S, et al (2014) Searching for missing heritability: Designing rare variant association studies. PNAS 17: E455–E464. [OpenAIRE]

9 Cirulli ET, Goldstein DB (2010) Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet 11: 415 10.1038/nrg2779 20479773 [OpenAIRE] [PubMed] [DOI]

10 Gusev A, Hong Lee S, Trynka G, Finucane H, Vilhjálmsson BJ, Xu H, et al (2014) Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases. Amer. J. Human Genet 95: 535–552.25439723 [OpenAIRE] [PubMed]

11 Zuk O, Hechter E, Sunyaev SR, Lander ES (2012) The mystery of missing heritability: genetic interaction create phantom heritability. PNAS 109(4): 1193–1198. 10.1073/pnas.1119675109 22223662 [OpenAIRE] [PubMed] [DOI]

12 Daetwyler HD, Capitan A, Pausch H, Stothard P, van Binsbergen R, Brondum RF, et al 2014 Whole genome sequencing of 234 bulls facilitates mapping of monogenic and complex traits in cattle. Nat Genet 10.1038/ng.3034 [OpenAIRE] [DOI]

13 Meacham F, Boffelli D, Dhahbi J, Martin DI, Singer M, Pachter L (2011) Identification and correction of systematic error in high-throughput sequence data. BMC Bioinformatics 12: 451 10.1186/1471-2105-12-451 22099972 [OpenAIRE] [PubMed] [DOI]

14 Loman NJ, Misra RV, Dallman TJ, Constantinidou C, Gharbia SE, Wain J, et al (2012) Performance comparison of benchtop high-throughput sequencing platforms. Nat. Biotechnol 30 (5): 434–439. ISSN 1087-0156. 10.1038/nbt.2198 22522955 [OpenAIRE] [PubMed] [DOI]

15 Meuwissen THE, Hayes BJ, Goddard ME (2001) Prediction of total genetic value using genome-wide dense marker maps. Genet 157: 1819–1829.

51 references, page 1 of 4
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