A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis

L Madireddy; NA Patsopoulos; C Cotsapas; SD Bos; A Beecham; J McCauley; K Kim; XM Jia; A Santaniello; SJ Caillier; TFM Andlauer; LF Barcellos; T Berge; L Bernardinelli; F Martinelli-Boneschi; DR Booth; F Briggs; EG Celius; M Comabella; G Comi; BAC Cree; Sandra D'ALFONSO; K Dedham; P Duquette; D Efthimios; F Esposito; B Fontaine; C Gasperi; A Goris; B Dubois; PA Gourraud; G Hadjigeorgiou; J Haines; C Hawkins; B Hemmer; R Hintzen; D Horakova; N Isobe; S Kalra; J Kira; M Khalil; I Kockum; CM Lill; MR Lincoln; F Luessi; R Martin; A Oturai; A Palotie; MA Pericak-Vance; R Henry; J Saarela; A Ivinson; T Olsson; BV Taylor; GJ Stewart; HF Harbo; A Compston; SL Hauser; DA Hafler; F Zipp; P De Jager; S Sawcer; JR Oksenberg; SE Baranzini

doi:10.1038/s41467-019-09773-y

A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis

L Madireddy
, NA Patsopoulos
, C Cotsapas
, SD Bos
, A Beecham
, J McCauley
, K Kim
, XM Jia
, A Santaniello
, SJ Caillier
, TFM Andlauer
, LF Barcellos
, T Berge
, L Bernardinelli
, F Martinelli-Boneschi
, DR Booth
, F Briggs
, EG Celius
, M Comabella
, G Comi

BAC Cree, Sandra D'ALFONSO, K Dedham, P Duquette, D Efthimios, F Esposito, B Fontaine, C Gasperi, A Goris, B Dubois, PA Gourraud, G Hadjigeorgiou, J Haines, C Hawkins, B Hemmer, R Hintzen, D Horakova, N Isobe, S Kalra, J Kira, M Khalil, I Kockum, CM Lill, MR Lincoln, F Luessi, R Martin, A Oturai, A Palotie, MA Pericak-Vance, R Henry, J Saarela, A Ivinson, T Olsson, BV Taylor, GJ Stewart, HF Harbo, A Compston, SL Hauser, DA Hafler, F Zipp, P De Jager, S Sawcer, JR Oksenberg, SE Baranzini

Dipartimento di Scienze della Salute

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intraindividual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available.

Lingua originale	Inglese
pagine (da-a)	2236
Rivista	Nature Communications
Volume	10
Numero di pubblicazione	1
DOI	https://doi.org/10.1038/s41467-019-09773-y
Stato di pubblicazione	Pubblicato - 2019

Keywords

Gene Expression Regulation
Genes, Regulator
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Multiple Sclerosis
Polymorphism, Single Nucleotide
Systems Biology

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10.1038/s41467-019-09773-y

http://hdl.handle.net/11579/112443

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Madireddy, L., Patsopoulos, NA., Cotsapas, C., Bos, SD., Beecham, A., McCauley, J., Kim, K., Jia, XM., Santaniello, A., Caillier, SJ., Andlauer, TFM., Barcellos, LF., Berge, T., Bernardinelli, L., Martinelli-Boneschi, F., Booth, DR., Briggs, F., Celius, EG., Comabella, M., ... Baranzini, SE. (2019). A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis. Nature Communications, 10(1), 2236. https://doi.org/10.1038/s41467-019-09773-y

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abstract = "Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intraindividual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available.",

keywords = "Gene Expression Regulation, Genes, Regulator, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Multiple Sclerosis, Polymorphism, Single Nucleotide, Systems Biology, Gene Expression Regulation, Genes, Regulator, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Multiple Sclerosis, Polymorphism, Single Nucleotide, Systems Biology",

author = "L Madireddy and NA Patsopoulos and C Cotsapas and SD Bos and A Beecham and J McCauley and K Kim and XM Jia and A Santaniello and SJ Caillier and TFM Andlauer and LF Barcellos and T Berge and L Bernardinelli and F Martinelli-Boneschi and DR Booth and F Briggs and EG Celius and M Comabella and G Comi and BAC Cree and Sandra D'ALFONSO and K Dedham and P Duquette and D Efthimios and F Esposito and B Fontaine and C Gasperi and A Goris and B Dubois and PA Gourraud and G Hadjigeorgiou and J Haines and C Hawkins and B Hemmer and R Hintzen and D Horakova and N Isobe and S Kalra and J Kira and M Khalil and I Kockum and CM Lill and MR Lincoln and F Luessi and R Martin and A Oturai and A Palotie and MA Pericak-Vance and R Henry and J Saarela and A Ivinson and T Olsson and BV Taylor and GJ Stewart and HF Harbo and A Compston and SL Hauser and DA Hafler and F Zipp and \{De Jager\}, P and S Sawcer and JR Oksenberg and SE Baranzini",

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doi = "10.1038/s41467-019-09773-y",

language = "English",

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pages = "2236",

journal = "Nature Communications",

issn = "2041-1723",

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Madireddy, L, Patsopoulos, NA, Cotsapas, C, Bos, SD, Beecham, A, McCauley, J, Kim, K, Jia, XM, Santaniello, A, Caillier, SJ, Andlauer, TFM, Barcellos, LF, Berge, T, Bernardinelli, L, Martinelli-Boneschi, F, Booth, DR, Briggs, F, Celius, EG, Comabella, M, Comi, G, Cree, BAC, D'ALFONSO, S, Dedham, K, Duquette, P, Efthimios, D, Esposito, F, Fontaine, B, Gasperi, C, Goris, A, Dubois, B, Gourraud, PA, Hadjigeorgiou, G, Haines, J, Hawkins, C, Hemmer, B, Hintzen, R, Horakova, D, Isobe, N, Kalra, S, Kira, J, Khalil, M, Kockum, I, Lill, CM, Lincoln, MR, Luessi, F, Martin, R, Oturai, A, Palotie, A, Pericak-Vance, MA, Henry, R, Saarela, J, Ivinson, A, Olsson, T, Taylor, BV, Stewart, GJ, Harbo, HF, Compston, A, Hauser, SL, Hafler, DA, Zipp, F, De Jager, P, Sawcer, S, Oksenberg, JR & Baranzini, SE 2019, 'A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis', Nature Communications, vol. 10, n. 1, pagg. 2236. https://doi.org/10.1038/s41467-019-09773-y

TY - JOUR

T1 - A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis

AU - Madireddy, L

AU - Patsopoulos, NA

AU - Cotsapas, C

AU - Bos, SD

AU - Beecham, A

AU - McCauley, J

AU - Kim, K

AU - Jia, XM

AU - Santaniello, A

AU - Caillier, SJ

AU - Andlauer, TFM

AU - Barcellos, LF

AU - Berge, T

AU - Bernardinelli, L

AU - Martinelli-Boneschi, F

AU - Booth, DR

AU - Briggs, F

AU - Celius, EG

AU - Comabella, M

AU - Comi, G

AU - Cree, BAC

AU - D'ALFONSO, Sandra

AU - Dedham, K

AU - Duquette, P

AU - Efthimios, D

AU - Esposito, F

AU - Fontaine, B

AU - Gasperi, C

AU - Goris, A

AU - Dubois, B

AU - Gourraud, PA

AU - Hadjigeorgiou, G

AU - Haines, J

AU - Hawkins, C

AU - Hemmer, B

AU - Hintzen, R

AU - Horakova, D

AU - Isobe, N

AU - Kalra, S

AU - Kira, J

AU - Khalil, M

AU - Kockum, I

AU - Lill, CM

AU - Lincoln, MR

AU - Luessi, F

AU - Martin, R

AU - Oturai, A

AU - Palotie, A

AU - Pericak-Vance, MA

AU - Henry, R

AU - Saarela, J

AU - Ivinson, A

AU - Olsson, T

AU - Taylor, BV

AU - Stewart, GJ

AU - Harbo, HF

AU - Compston, A

AU - Hauser, SL

AU - Hafler, DA

AU - Zipp, F

AU - De Jager, P

AU - Sawcer, S

AU - Oksenberg, JR

AU - Baranzini, SE

PY - 2019

Y1 - 2019

N2 - Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intraindividual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available.

AB - Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intraindividual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available.

KW - Gene Expression Regulation

KW - Genes, Regulator

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Multiple Sclerosis

KW - Polymorphism, Single Nucleotide

KW - Systems Biology

KW - Gene Expression Regulation

KW - Genes, Regulator

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Multiple Sclerosis

KW - Polymorphism, Single Nucleotide

KW - Systems Biology

UR - https://iris.uniupo.it/handle/11579/112443

U2 - 10.1038/s41467-019-09773-y

DO - 10.1038/s41467-019-09773-y

M3 - Article

SN - 2041-1723

VL - 10

SP - 2236

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis

Abstract

Keywords

OSS delle Nazioni Unite

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