The impact of sex on gene expression across human tissues.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
11 09 2020
11 09 2020
Historique:
received:
25
11
2019
accepted:
03
08
2020
entrez:
11
9
2020
pubmed:
12
9
2020
medline:
29
10
2020
Statut:
ppublish
Résumé
Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.
Identifiants
pubmed: 32913072
pii: 369/6509/eaba3066
doi: 10.1126/science.aba3066
pmc: PMC8136152
mid: NIHMS1687191
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIMH NIH HHS
ID : R01 MH107666
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109905
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH106842
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007598
Pays : United States
Organisme : NHGRI NIH HHS
ID : K99 HG009916
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142028
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG006855
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH090951
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG000044
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA229618
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000430
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG011138
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH104393
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG010480
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA006227
Pays : United States
Organisme : NHGRI NIH HHS
ID : U41 HG002371
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG008150
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG008901
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007593
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM124486
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH090936
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK110919
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG002585
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002550
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101820
Pays : United States
Organisme : NHGRI NIH HHS
ID : F32 HG009987
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG010067
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH090941
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM122924
Pays : United States
Organisme : NHGRI NIH HHS
ID : U41 HG009494
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101822
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH090937
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201000029C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101814
Pays : United States
Organisme : NHGRI NIH HHS
ID : R35 HG010718
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020595
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG003284
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM108711
Pays : United States
Investigateurs
François Aguet
(F)
Shankara Anand
(S)
Kristin G Ardlie
(KG)
Stacey Gabriel
(S)
Gad A Getz
(GA)
Aaron Graubert
(A)
Kane Hadley
(K)
Robert E Handsaker
(RE)
Katherine H Huang
(KH)
Seva Kashin
(S)
Xiao Li
(X)
Daniel G MacArthur
(DG)
Samuel R Meier
(SR)
Jared L Nedzel
(JL)
Duyen T Nguyen
(DT)
Ayellet V Segrè
(AV)
Ellen Todres
(E)
Brunilda Balliu
(B)
Alvaro N Barbeira
(AN)
Alexis Battle
(A)
Rodrigo Bonazzola
(R)
Andrew Brown
(A)
Christopher D Brown
(CD)
Stephane E Castel
(SE)
Donald F Conrad
(DF)
Daniel J Cotter
(DJ)
Nancy Cox
(N)
Sayantan Das
(S)
Olivia M de Goede
(OM)
Emmanouil T Dermitzakis
(ET)
Jonah Einson
(J)
Barbara E Engelhardt
(BE)
Eleazar Eskin
(E)
Tiffany Y Eulalio
(TY)
Nicole M Ferraro
(NM)
Elise D Flynn
(ED)
Laure Fresard
(L)
Eric R Gamazon
(ER)
Diego Garrido-Martín
(D)
Nicole R Gay
(NR)
Michael J Gloudemans
(MJ)
Roderic Guigó
(R)
Andrew R Hame
(AR)
Yuan He
(Y)
Paul J Hoffman
(PJ)
Farhad Hormozdiari
(F)
Lei Hou
(L)
Hae Kyung Im
(HK)
Brian Jo
(B)
Silva Kasela
(S)
Manolis Kellis
(M)
Sarah Kim-Hellmuth
(S)
Alan Kwong
(A)
Tuuli Lappalainen
(T)
Xin Li
(X)
Yanyu Liang
(Y)
Serghei Mangul
(S)
Pejman Mohammadi
(P)
Stephen B Montgomery
(SB)
Manuel Muñoz-Aguirre
(M)
Daniel C Nachun
(DC)
Andrew B Nobel
(AB)
Meritxell Oliva
(M)
YoSon Park
(Y)
Yongjin Park
(Y)
Princy Parsana
(P)
Abhiram S Rao
(AS)
Ferran Reverter
(F)
John M Rouhana
(JM)
Chiara Sabatti
(C)
Ashis Saha
(A)
Matthew Stephens
(M)
Barbara E Stranger
(BE)
Benjamin J Strober
(BJ)
Nicole A Teran
(NA)
Ana Viñuela
(A)
Gao Wang
(G)
Xiaoquan Wen
(X)
Fred Wright
(F)
Valentin Wucher
(V)
Yuxin Zou
(Y)
Pedro G Ferreira
(PG)
Gen Li
(G)
Marta Melé
(M)
Esti Yeger-Lotem
(E)
Mary E Barcus
(ME)
Debra Bradbury
(D)
Tanya Krubit
(T)
Jeffrey A McLean
(JA)
Liqun Qi
(L)
Karna Robinson
(K)
Nancy V Roche
(NV)
Anna M Smith
(AM)
Leslie Sobin
(L)
David E Tabor
(DE)
Anita Undale
(A)
Jason Bridge
(J)
Lori E Brigham
(LE)
Barbara A Foster
(BA)
Bryan M Gillard
(BM)
Richard Hasz
(R)
Marcus Hunter
(M)
Christopher Johns
(C)
Mark Johnson
(M)
Ellen Karasik
(E)
Gene Kopen
(G)
William F Leinweber
(WF)
Alisa McDonald
(A)
Michael T Moser
(MT)
Kevin Myer
(K)
Kimberley D Ramsey
(KD)
Brian Roe
(B)
Saboor Shad
(S)
Jeffrey A Thomas
(JA)
Gary Walters
(G)
Michael Washington
(M)
Joseph Wheeler
(J)
Scott D Jewell
(SD)
Daniel C Rohrer
(DC)
Dana R Valley
(DR)
David A Davis
(DA)
Deborah C Mash
(DC)
Philip A Branton
(PA)
Laura K Barker
(LK)
Heather M Gardiner
(HM)
Maghboeba Mosavel
(M)
Laura A Siminoff
(LA)
Paul Flicek
(P)
Maximilian Haeussler
(M)
Thomas Juettemann
(T)
W James Kent
(WJ)
Christopher M Lee
(CM)
Conner C Powell
(CC)
Kate R Rosenbloom
(KR)
Magali Ruffier
(M)
Dan Sheppard
(D)
Kieron Taylor
(K)
Stephen J Trevanion
(SJ)
Daniel R Zerbino
(DR)
Nathan S Abell
(NS)
Joshua Akey
(J)
Lin Chen
(L)
Kathryn Demanelis
(K)
Jennifer A Doherty
(JA)
Andrew P Feinberg
(AP)
Kasper D Hansen
(KD)
Peter F Hickey
(PF)
Farzana Jasmine
(F)
Lihua Jiang
(L)
Rajinder Kaul
(R)
Muhammad G Kibriya
(MG)
Jin Billy Li
(JB)
Qin Li
(Q)
Shin Lin
(S)
Sandra E Linder
(SE)
Brandon L Pierce
(BL)
Lindsay F Rizzardi
(LF)
Andrew D Skol
(AD)
Kevin S Smith
(KS)
Michael Snyder
(M)
John Stamatoyannopoulos
(J)
Hua Tang
(H)
Meng Wang
(M)
Latarsha J Carithers
(LJ)
Ping Guan
(P)
Susan E Koester
(SE)
A Roger Little
(AR)
Helen M Moore
(HM)
Concepcion R Nierras
(CR)
Abhi K Rao
(AK)
Jimmie B Vaught
(JB)
Simona Volpi
(S)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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