Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
To extend our understanding of the genetic basis of human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study of purified CD4(+) T cells and monocytes, representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. Context-specific cis- and trans-eQTLs were identified, and cross-population mapping allowed, in some cases, putative functional assignment of candidate causal regulatory variants for disease-associated loci. We note an over-representation of T cell-specific eQTLs among susceptibility alleles for autoimmune diseases and of monocyte-specific eQTLs among Alzheimer's and Parkinson's disease variants. This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants.
Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, MA 02115, USA.
Towfique
T
Raj
Katie
K
Rothamel
Sara
S
Mostafavi
Chun
C
Ye
Mark N
MN
Lee
Joseph M
JM
Replogle
Ting
T
Feng
Michelle
M
Lee
Natasha
N
Asinovski
Irene
I
Frohlich
Selina
S
Imboywa
Alina
A
Von Korff
Yukinori
Y
Okada
Nikolaos A
NA
Patsopoulos
Scott
S
Davis
Cristin
C
McCabe
Hyun-il
HI
Paik
Gyan P
GP
Srivastava
Soumya
S
Raychaudhuri
David A
DA
Hafler
Daphne
D
Koller
Aviv
A
Regev
Nir
N
Hacohen
Diane
D
Mathis
Christophe
C
Benoist
Barbara E
BE
Stranger
Philip L
PL
De Jager
D056704:Adaptive Immunity / Q000235:genetics; D000483:Alleles; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics; D001327:Autoimmune Diseases / Q000208:ethnology / Q000235:genetics*; D015551:Autoimmunity / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005006:Ethnicity / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D009000:Monocytes / Q000276:immunology*; D009103:Multiple Sclerosis / Q000208:ethnology / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000208:ethnology / Q000235:genetics*; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012213:Rheumatic Fever / Q000208:ethnology / Q000235:genetics; D059467:Transcriptome