title: Heritability and genomics of gene expression in peripheral blood.
abstract: We assessed gene expression profiles in 2,752 twins, using a classic twin design to quantify expression heritability and quantitative trait loci (eQTLs) in peripheral blood. The most highly heritable genes (∼777) were grouped into distinct expression clusters, enriched in gene-poor regions, associated with specific gene function or ontology classes, and strongly associated with disease designation. The design enabled a comparison of twin-based heritability to estimates based on dizygotic identity-by-descent sharing and distant genetic relatedness. Consideration of sampling variation suggests that previous heritability estimates have been upwardly biased. Genotyping of 2,494 twins enabled powerful identification of eQTLs, which we further examined in a replication set of 1,895 unrelated subjects. A large number of non-redundant local eQTLs (6,756) met replication criteria, whereas a relatively small number of distant eQTLs (165) met quality control and replication standards. Our results provide a new resource toward understanding the genetic control of transcription.
authors.affiliation: 1] Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA. [2] Department of Statistics, North Carolina State University, Raleigh, North Carolina, USA. [3] Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, USA. [4].
authors.forename: Fred A
authors.initials: FA
authors.lastname: Wright
authors.affiliation: 1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [2].
authors.forename: Patrick F
authors.identifier: 000000026619873X
authors.initials: PF
authors.lastname: Sullivan
authors.affiliation: Department of Genetics, Rutgers University, New Brunswick, New Jersey, USA.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Brooks
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Xia
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Vered
authors.initials: V
authors.lastname: Madar
authors.affiliation: Department of Psychiatry, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: Jansen
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Wonil
authors.initials: W
authors.lastname: Chung
authors.affiliation: 1] Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA. [2] Department of Statistics, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Zhou
authors.affiliation: Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
authors.forename: Abdel
authors.initials: A
authors.lastname: Abdellaoui
authors.affiliation: Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Batista
authors.affiliation: Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Butler
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Guanhua
authors.identifier: 0000000293142037
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Ting-Huei
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Environmental and Occupational Health Sciences Institute, Rutgers University, New Brunswick, New Jersey, USA.
authors.forename: David
authors.initials: D
authors.lastname: D'Ambrosio
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Gallins
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Min Jin
authors.initials: MJ
authors.lastname: Ha
authors.affiliation: Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
authors.forename: Jouke Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.affiliation: Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Shunping
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
authors.forename: Mathijs
authors.initials: M
authors.lastname: Kattenberg
authors.affiliation: Environmental and Occupational Health Sciences Institute, Rutgers University, New Brunswick, New Jersey, USA.
authors.forename: Jaspreet
authors.initials: J
authors.lastname: Kochar
authors.affiliation: Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
authors.forename: Christel M
authors.initials: CM
authors.lastname: Middeldorp
authors.affiliation: Environmental and Occupational Health Sciences Institute, Rutgers University, New Brunswick, New Jersey, USA.
authors.forename: Ani
authors.initials: A
authors.lastname: Qu
authors.affiliation: Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Andrey
authors.initials: A
authors.lastname: Shabalin
authors.affiliation: Department of Genetics, Rutgers University, New Brunswick, New Jersey, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Tischfield
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Todd
authors.affiliation: 1] Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA. [2] Department of Statistics, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Jung-Ying
authors.initials: JY
authors.lastname: Tzeng
authors.affiliation: Department of Psychiatry, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: van Grootheest
authors.affiliation: Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Vink
authors.affiliation: Environmental and Occupational Health Sciences Institute, Rutgers University, New Brunswick, New Jersey, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Computer Science, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Weibo
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.affiliation: Department of Psychiatry, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Smit
authors.affiliation: Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
authors.forename: Eco J
authors.initials: EJ
authors.lastname: de Geus
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Psychiatry, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
mesh_terms: D001769:Blood / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D016013:Likelihood Functions; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*
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