Genetic variants regulating immune cell levels in health and disease.

Details

Serval ID
serval:BIB_875DB36AB649
Type
Article: article from journal or magazin.
Collection
Publications
Title
Genetic variants regulating immune cell levels in health and disease.
Journal
Cell
Author(s)
Orrù V., Steri M., Sole G., Sidore C., Virdis F., Dei M., Lai S., Zoledziewska M., Busonero F., Mulas A., Floris M., Mentzen W.I., Urru S.A., Olla S., Marongiu M., Piras M.G., Lobina M., Maschio A., Pitzalis M., Urru M.F., Marcelli M., Cusano R., Deidda F., Serra V., Oppo M., Pilu R., Reinier F., Berutti R., Pireddu L., Zara I., Porcu E., Kwong A., Brennan C., Tarrier B., Lyons R., Kang H.M., Uzzau S., Atzeni R., Valentini M., Firinu D., Leoni L., Rotta G., Naitza S., Angius A., Congia M., Whalen M.B., Jones C.M., Schlessinger D., Abecasis G.R., Fiorillo E., Sanna S., Cucca F.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
26/09/2013
Peer-reviewed
Oui
Volume
155
Number
1
Pages
242-256
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The complex network of specialized cells and molecules in the immune system has evolved to defend against pathogens, but inadvertent immune system attacks on "self" result in autoimmune disease. Both genetic regulation of immune cell levels and their relationships with autoimmunity are largely undetermined. Here, we report genetic contributions to quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages. We first estimated trait heritability, showing that it can be substantial, accounting for up to 87% of the variance (mean 41%). Next, by assessing ∼8.2 million variants that we identified and confirmed in an extended set of 2,870 individuals, 23 independent variants at 13 loci associated with at least one trait. Notably, variants at three loci (HLA, IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease associations. These results connect specific cellular phenotypes to specific genetic variants, helping to explicate their involvement in disease.
Keywords
Flow Cytometry/methods, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Immune System Diseases/genetics, Phenotype, Polymorphism, Single Nucleotide
Pubmed
Web of science
Open Access
Yes
Create date
18/01/2021 21:41
Last modification date
19/01/2021 6:26
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