Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
30333196
TITLE
Cell-type-specific eQTL of primary melanocytes facilitates identification of melanoma susceptibility genes.
ABSTRACT
Most expression quantitative trait locus (eQTL) studies to date have been performed in heterogeneous tissues as opposed to specific cell types. To better understand the cell-type-specific regulatory landscape of human melanocytes, which give rise to melanoma but account for <5% of typical human skin biopsies, we performed an eQTL analysis in primary melanocyte cultures from 106 newborn males. We identified 597,335 -eQTL SNPs prior to linkage disequilibrium (LD) pruning and 4997 eGenes (FDR < 0.05). Melanocyte eQTLs differed considerably from those identified in the 44 GTEx tissue types, including skin. Over a third of melanocyte eGenes, including key genes in melanin synthesis pathways, were unique to melanocytes compared to those of GTEx skin tissues or TCGA melanomas. The melanocyte data set also identified -eQTLs, including those connecting a pigmentation-associated functional SNP with four genes, likely through -regulation of Melanocyte eQTLs are enriched in -regulatory signatures found in melanocytes as well as in melanoma-associated variants identified through genome-wide association studies. Melanocyte eQTLs also colocalized with melanoma GWAS variants in five known loci. Finally, a transcriptome-wide association study using melanocyte eQTLs uncovered four novel susceptibility loci, where imputed expression levels of five genes ( , , , , and ) were associated with melanoma at genome-wide significant -values. Our data highlight the utility of lineage-specific eQTL resources for annotating GWAS findings, and present a robust database for genomic research of melanoma risk and melanocyte biology.
2018 Zhang et al.; Published by Cold Spring Harbor Laboratory Press.
DATE PUBLISHED
2018 11
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2017/12/07
accepted 2018/09/21
pmc-release 2019/05/01
pubmed 2018/10/20 06:00
medline 2018/10/20 06:00
entrez 2018/10/19 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Zhang T Zhang Tongwu T Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Choi J Choi Jiyeon J Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kovacs MA Kovacs Michael A MA Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Shi J Shi Jianxin J Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Xu M Xu Mai M Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
NISC Comparative Sequencing Program
Melanoma Meta-Analysis Consortium
Goldstein AM Goldstein Alisa M AM Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Trower AJ Trower Adam J AJ Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, LS9 7TF, United Kingdom.
Bishop DT Bishop D Timothy DT Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, LS9 7TF, United Kingdom.
Iles MM Iles Mark M MM Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, LS9 7TF, United Kingdom.
Duffy DL Duffy David L DL Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4006, Australia.
MacGregor S MacGregor Stuart S Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4006, Australia.
Amundadottir LT Amundadottir Laufey T LT Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Law MH Law Matthew H MH Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4006, Australia.
Loftus SK Loftus Stacie K SK Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Pavan WJ Pavan William J WJ Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Brown KM Brown Kevin M KM Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Law Matthew H MH
Bishop D Timothy DT
Lee Jeffrey E JE
Brossard Myriam M
Martin Nicholas G NG
Moses Eric K EK
Song Fengju F
Barrett Jennifer H JH
Kumar Rajiv R
Easton Douglas F DF
Pharoah Paul D P PDP
Swerdlow Anthony J AJ
Kypreou Katerina P KP
Taylor John C JC
Harland Mark M
Randerson-Moor Juliette J
Akslen Lars A LA
Andresen Per A PA
Avril Marie-Françoise MF
Azizi Esther E
Scarrà Giovanna Bianchi GB
Brown Kevin M KM
Dȩbniak Tadeusz T
Duffy David L DL
Elder David E DE
Fang Shenying S
Friedman Eitan E
Galan Pilar P
Ghiorzo Paola P
Gillanders Elizabeth M EM
Goldstein Alisa M AM
Gruis Nelleke A NA
Hansson Johan J
Helsing Per P
Hočevar Marko M
Höiom Veronica V
Ingvar Christian C
Kanetsky Peter A PA
Chen Wei V WV
Landi Maria Teresa MT
Lang Julie J
Lathrop G Mark GM
Lubiński Jan J
Mackie Rona M RM
Mann Graham J GJ
Molven Anders A
Montgomery Grant W GW
Novaković Srdjan S
Olsson Håkan H
Puig Susana S
Puig-Butille Joan Anton JA
Wu Wenting W
Qureshi Abrar A AA
Radford-Smith Graham L GL
van der Stoep Nienke N
van Doorn Remco R
Whiteman David C DC
Craig Jamie E JE
Schadendorf Dirk D
Simms Lisa A LA
Burdon Kathryn P KP
Nyholt Dale R DR
Pooley Karen A KA
Orr Nick N
Stratigos Alexander J AJ
Cust Anne E AE
Ward Sarah V SV
Hayward Nicholas K NK
Han Jiali J
Schulze Hans-Joachim HJ
Dunning Alison M AM
Bishop Julia A Newton JAN
Demenais Florence F
Amos Christopher I CI
MacGregor Stuart S
Iles Mark M MM
Barnabas Beatrice B BB
Bouffard Gerard G GG
Brooks Shelis Y SY
Coleman Holly H
Dekhtyar Lyudmila L
Guan Xiaobin X
Han Joel J
Ho Shi-Ling SL
Legaspi Richelle R
Maduro Quino L QL
Masiello Catherine A CA
McDowell Jennifer C JC
Montemayor Casandra C
Mullikin James C JC
Park Morgan M
Riebow Nancy L NL
Schandler Karen K
Schmidt Brian B
Sison Christina C
Smith Raymond R
Stantripop Sirintorn S
Thomas James W JW
Thomas Pamela J PJ
Vemulapalli Meghana M
Young Alice C AC
JOURNAL
VOLUME: 28
ISSUE: 11
TITLE: Genome research
ISOABBREVIATION: Genome Res.
YEAR: 2018
MONTH: 11
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1549-5469
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Genome Res
COUNTRY: United States
ISSNLINKING: 1088-9051
NLMUNIQUEID: 9518021
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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R01 CA133996 NCI NIH HHS United States
R01 CA083115 NCI NIH HHS United States
P50 CA097007 NCI NIH HHS United States
R01 ES011740 NIEHS NIH HHS United States
P50 CA093459 NCI NIH HHS United States
C588/A19167 Cancer Research UK United Kingdom
C588/A4994 Cancer Research UK United Kingdom
C588/A10589 Cancer Research UK United Kingdom
C8216/A6129 Cancer Research UK United Kingdom
C490/A10124 Cancer Research UK United Kingdom
C1287/A10118 Cancer Research UK United Kingdom
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