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Genetics of gene expression in primary immune cells identifies cell type–specific master regulators and roles of HLA alleles | Nature Genetics
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Expression quantitative trait loci (eQTLs) are the genetic units of gene expression variation. Julian Knight and colleagues report an analysis of cell type–specific eQTLs from positively purified primary monocytes and B cells. Among the trans-acting eQTLs identified, they report new master regulators of gene expression, as well as autoimmune disease associations to specific HLA alleles. Trans-acting genetic variants have a substantial, albeit poorly characterized, role in the heritable determination of gene expression. Using paired purified primary monocytes and B cells, we identify new predominantly cell type–specific cis and trans expression quantitative trait loci (eQTLs), including multi-locus trans associations to LYZ and KLF4 in monocytes and B cells, respectively. Additionally, we observe a B cell–specific trans association of rs11171739 at 12q13.2, a known autoimmune disease locus, with IP6K2 (P = 5.8 × 10−15), PRIC285 (P = 3.0 × 10−10) and an upstream region of CDKN1A (P = 2 × 10−52), suggesting roles for cell cycle regulation and peroxisome proliferator-activated receptor γ (PPARγ) signaling in autoimmune pathogenesis. We also find that specific human leukocyte antigen (HLA) alleles form trans associations with the expression of AOAH and ARHGAP24 in monocytes but not in B cells. In summary, we show that mapping gene expression in defined primary cell populations identifies new cell type–specific trans-regulated networks and provides insights into the genetic basis of disease susceptibility.
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headline:Genetics of gene expression in primary immune cells identifies cell typeâspecific master regulators and roles of HLA alleles
description:Expression quantitative trait loci (eQTLs) are the genetic units of gene expression variation. Julian Knight and colleagues report an analysis of cell typeâspecific eQTLs from positively purified primary monocytes and B cells. Among the trans-acting eQTLs identified, they report new master regulators of gene expression, as well as autoimmune disease associations to specific HLA alleles. Trans-acting genetic variants have a substantial, albeit poorly characterized, role in the heritable determination of gene expression. Using paired purified primary monocytes and B cells, we identify new predominantly cell typeâspecific cis and trans expression quantitative trait loci (eQTLs), including multi-locus trans associations to LYZ and KLF4 in monocytes and B cells, respectively. Additionally, we observe a B cellâspecific trans association of rs11171739 at 12q13.2, a known autoimmune disease locus, with IP6K2 (P = 5.8 à 10â15), PRIC285 (P = 3.0 à 10â10) and an upstream region of CDKN1A (P = 2 à 10â52), suggesting roles for cell cycle regulation and peroxisome proliferator-activated receptor γ (PPARγ) signaling in autoimmune pathogenesis. We also find that specific human leukocyte antigen (HLA) alleles form trans associations with the expression of AOAH and ARHGAP24 in monocytes but not in B cells. In summary, we show that mapping gene expression in defined primary cell populations identifies new cell typeâspecific trans-regulated networks and provides insights into the genetic basis of disease susceptibility.
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Disease genetics
Functional genomics
Gene expression
Quantitative trait
Biomedicine
general
Human Genetics
Cancer Research
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Gene Function
Animal Genetics and Genomics
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headline:Genetics of gene expression in primary immune cells identifies cell typeâspecific master regulators and roles of HLA alleles
description:Expression quantitative trait loci (eQTLs) are the genetic units of gene expression variation. Julian Knight and colleagues report an analysis of cell typeâspecific eQTLs from positively purified primary monocytes and B cells. Among the trans-acting eQTLs identified, they report new master regulators of gene expression, as well as autoimmune disease associations to specific HLA alleles. Trans-acting genetic variants have a substantial, albeit poorly characterized, role in the heritable determination of gene expression. Using paired purified primary monocytes and B cells, we identify new predominantly cell typeâspecific cis and trans expression quantitative trait loci (eQTLs), including multi-locus trans associations to LYZ and KLF4 in monocytes and B cells, respectively. Additionally, we observe a B cellâspecific trans association of rs11171739 at 12q13.2, a known autoimmune disease locus, with IP6K2 (P = 5.8 à 10â15), PRIC285 (P = 3.0 à 10â10) and an upstream region of CDKN1A (P = 2 à 10â52), suggesting roles for cell cycle regulation and peroxisome proliferator-activated receptor γ (PPARγ) signaling in autoimmune pathogenesis. We also find that specific human leukocyte antigen (HLA) alleles form trans associations with the expression of AOAH and ARHGAP24 in monocytes but not in B cells. In summary, we show that mapping gene expression in defined primary cell populations identifies new cell typeâspecific trans-regulated networks and provides insights into the genetic basis of disease susceptibility.
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