Home LiteratureArticle Details
PMID: 21383966 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Single-tissue and cross-tissue heritability of gene expression via identity-by-descent in related or unrelated individuals.

PLoS genetics ·Vol. 7 ·No. 2 ·2011-02-00 ·Pages e1001317

Price AL, Helgason A, Thorleifsson G, McCarroll SA, Kong A, Stefansson K

Abstract

Family studies of individual tissues have shown that gene expression traits are genetically heritable. Here, we investigate cis and trans components of heritability both within and across tissues by applying variance-components methods to 722 Icelanders from family cohorts, using identity-by-descent (IBD) estimates from long-range phased genome-wide SNP data and gene expression measurements for approximately 19,000 genes in blood and adipose tissue. We estimate the proportion of gene expression heritability attributable to cis regulation as 37% in blood and 24% in adipose tissue. Our results indicate that the correlation in gene expression measurements across these tissues is primarily due to heritability at cis loci, whereas there is little sharing of trans regulation across tissues. One implication of this finding is that heritability in tissues composed of heterogeneous cell types is expected to be more dominated by cis regulation than in tissues composed of more homogeneous cell types, consistent with our blood versus adipose results as well as results of previous studies in lymphoblastoid cell lines. Finally, we obtained similar estimates of the cis components of heritability using IBD between unrelated individuals, indicating that transgenerational epigenetic inheritance does not contribute substantially to the "missing heritability" of gene expression in these tissue types.

MeSH Terms
Epigenesis, Genetic Female Gene Expression Gene Expression Regulation Humans Male
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Price Alkes L
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America. aprice@hsph.harvard.edu
Helgason Agnar
Thorleifsson Gudmar
McCarroll Steven A
Kong Augustine
Stefansson Kari
Conflict of Interest

Authors whose affiliations are listed as deCODE Genetics are shareholders and/or employees of deCODE Genetics, a biotechnology company.

References (46)
46 references, click to expand
  1. Genetics of gene expression and its effect on disease.
    Nature. 2008 Mar 27;452(7186):423-8 PMID: 18344981
  2. An association between the kinship and fertility of human couples.
    Science. 2008 Feb 8;319(5864):813-6 PMID: 18258915
  3. Effects of cis and trans genetic ancestry on gene expression in African Americans.
    PLoS Genet. 2008 Dec;4(12):e1000294 PMID: 19057673
  4. Robust variance-components approach for assessing genetic linkage in pedigrees.
    Am J Hum Genet. 1994 Mar;54(3):535-43 PMID: 8116623
  5. Integrating common and rare genetic variation in diverse human populations.
    Nature. 2010 Sep 2;467(7311):52-8 PMID: 20811451
  6. Heritability in the genomics era--concepts and misconceptions.
    Nat Rev Genet. 2008 Apr;9(4):255-66 PMID: 18319743
  7. Variations in the cell-content and chemical composition of the human blood due to age, sex and season.
    Scand J Clin Lab Invest. 1952;4(3):216-36 PMID: 13014995
  8. Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission.
    Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2538-43 PMID: 12601169
  9. Reconciling the analysis of IBD and IBS in complex trait studies.
    Nat Rev Genet. 2010 Nov;11(11):800-5 PMID: 20877324
  10. Whole population, genome-wide mapping of hidden relatedness.
    Genome Res. 2009 Feb;19(2):318-26 PMID: 18971310
  11. Variance component model to account for sample structure in genome-wide association studies.
    Nat Genet. 2010 Apr;42(4):348-54 PMID: 20208533
  12. Polymorphic cis- and trans-regulation of human gene expression.
    PLoS Biol. 2010 Sep 14;8(9): PMID: 20856902
  13. Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution.
    Q Rev Biol. 2009 Jun;84(2):131-76 PMID: 19606595
  14. Geographical genomics of human leukocyte gene expression variation in southern Morocco.
    Nat Genet. 2010 Jan;42(1):62-7 PMID: 19966804
  15. A second generation human haplotype map of over 3.1 million SNPs.
    Nature. 2007 Oct 18;449(7164):851-61 PMID: 17943122
  16. Common regulatory variation impacts gene expression in a cell type-dependent manner.
    Science. 2009 Sep 4;325(5945):1246-50 PMID: 19644074
  17. Missing heritability and strategies for finding the underlying causes of complex disease.
    Nat Rev Genet. 2010 Jun;11(6):446-50 PMID: 20479774
  18. Patterns of cis regulatory variation in diverse human populations.
    PLoS Genet. 2012;8(4):e1002639 PMID: 22532805
  19. Mapping complex disease traits with global gene expression.
    Nat Rev Genet. 2009 Mar;10(3):184-94 PMID: 19223927
  20. Detection of sharing by descent, long-range phasing and haplotype imputation.
    Nat Genet. 2008 Sep;40(9):1068-75 PMID: 19165921
  21. Genetic analysis of genome-wide variation in human gene expression.
    Nature. 2004 Aug 12;430(7001):743-7 PMID: 15269782
  22. Replicated effects of sex and genotype on gene expression in human lymphoblastoid cell lines.
    Hum Mol Genet. 2007 Feb 15;16(4):364-73 PMID: 17164263
  23. New insights into the genetic control of gene expression using a Bayesian multi-tissue approach.
    PLoS Comput Biol. 2010 Apr 08;6(4):e1000737 PMID: 20386736
  24. Cell type-specific gene expression differences in complex tissues.
    Nat Methods. 2010 Apr;7(4):287-9 PMID: 20208531
  25. Heritability and tissue specificity of expression quantitative trait loci.
    PLoS Genet. 2006 Oct 20;2(10):e172 PMID: 17054398
  26. Genome-wide association studies: potential next steps on a genetic journey.
    Hum Mol Genet. 2008 Oct 15;17(R2):R156-65 PMID: 18852205
  27. DNA methylation profiles in monozygotic and dizygotic twins.
    Nat Genet. 2009 Feb;41(2):240-5 PMID: 19151718
  28. Population genomics of human gene expression.
    Nat Genet. 2007 Oct;39(10):1217-24 PMID: 17873874
  29. Revealing the architecture of gene regulation: the promise of eQTL studies.
    Trends Genet. 2008 Aug;24(8):408-15 PMID: 18597885
  30. Bias, precision and heritability of self-reported and clinically measured height in Australian twins.
    Hum Genet. 2006 Nov;120(4):571-80 PMID: 16933140
  31. A genome-wide association study of global gene expression.
    Nat Genet. 2007 Oct;39(10):1202-7 PMID: 17873877
  32. "In vitro" and multicolor phenotypic characterization of cell subpopulations identified in fresh human adipose tissue stromal vascular fraction and in the derived mesenchymal stem cells.
    J Transl Med. 2007 Oct 31;5:55 PMID: 17974012
  33. Transgenerational epigenetic effects.
    Annu Rev Genomics Hum Genet. 2008;9:233-57 PMID: 18767965
  34. Complex trait analysis of gene expression uncovers polygenic and pleiotropic networks that modulate nervous system function.
    Nat Genet. 2005 Mar;37(3):233-42 PMID: 15711545
  35. Personal genomes: The case of the missing heritability.
    Nature. 2008 Nov 6;456(7218):18-21 PMID: 18987709
  36. Normalization procedures and detection of linkage signal in genetical-genomics experiments.
    Nat Genet. 2006 Aug;38(8):855-6; author reply 856-9 PMID: 16874319
  37. Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines.
    PLoS Genet. 2008 Nov;4(11):e1000287 PMID: 19043577
  38. Genetics of gene expression surveyed in maize, mouse and man.
    Nature. 2003 Mar 20;422(6929):297-302 PMID: 12646919
  39. Finding the missing heritability of complex diseases.
    Nature. 2009 Oct 8;461(7265):747-53 PMID: 19812666
  40. Mapping the genetic architecture of gene expression in human liver.
    PLoS Biol. 2008 May 6;6(5):e107 PMID: 18462017
  41. Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings.
    PLoS Genet. 2006 Mar;2(3):e41 PMID: 16565746
  42. Common SNPs explain a large proportion of the heritability for human height.
    Nat Genet. 2010 Jul;42(7):565-9 PMID: 20562875
  43. Epigenetic inheritance at the agouti locus in the mouse.
    Nat Genet. 1999 Nov;23(3):314-8 PMID: 10545949
  44. Systematic haplotype analysis resolves a complex plasma plant sterol locus on the Micronesian Island of Kosrae.
    Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13886-91 PMID: 19667188
  45. Genetic inheritance of gene expression in human cell lines.
    Am J Hum Genet. 2004 Dec;75(6):1094-105 PMID: 15514893
  46. Genetics of human gene expression: mapping DNA variants that influence gene expression.
    Nat Rev Genet. 2009 Sep;10(9):595-604 PMID: 19636342
Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1001317
Email
aprice@hsph.harvard.edu
Published
2011-02-00
Epub
2011-00-24
Pages
e1001317
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC3044684
Subset
IM
Grants
NHGRI NIH HHS · R03 HG005732 · United States
NHGRI NIH HHS · R03HG005732 · United States
External Links
PubMed source DOI: 10.1371/journal.pgen.1001317 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2