@article {83,
	title = {Genetic regulatory variation in populations informs transcriptome analysis in rare disease.},
	journal = {Science},
	volume = {366},
	year = {2019},
	month = {2019 10 18},
	pages = {351-356},
	abstract = {<p>Transcriptome data can facilitate the interpretation of the effects of rare genetic variants. Here, we introduce ANEVA (analysis of expression variation) to quantify genetic variation in gene dosage from allelic expression (AE) data in a population. Application of ANEVA to the Genotype-Tissues Expression (GTEx) data showed that this variance estimate is robust and correlated with selective constraint in a gene. Using these variance estimates in a dosage outlier test (ANEVA-DOT) applied to AE data from 70 Mendelian muscular disease patients showed accuracy in detecting genes with pathogenic variants in previously resolved cases and led to one confirmed and several potential new diagnoses. Using our reference estimates from GTEx data, ANEVA-DOT can be incorporated in rare disease diagnostic pipelines to use RNA-sequencing data more effectively.</p>},
	issn = {1095-9203},
	doi = {10.1126/science.aay0256},
	author = {Mohammadi, Pejman and Castel, Stephane E and Cummings, Beryl B and Einson, Jonah and Sousa, Christina and Hoffman, Paul and Donkervoort, Sandra and Jiang, Zhuoxun and Mohassel, Payam and Foley, A Reghan and Wheeler, Heather E and Im, Hae Kyung and Bonnemann, Carsten G and MacArthur, Daniel G and Lappalainen, Tuuli}
}
@article {25,
	title = {Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations.},
	journal = {Nat Commun},
	volume = {8},
	year = {2017},
	month = {2017 08 16},
	pages = {266},
	abstract = {<p>The immune system plays a major role in human health and disease, and understanding genetic causes of interindividual variability of immune responses is vital. Here, we isolate monocytes from 134 genotyped individuals, stimulate these cells with three defined microbe-associated molecular patterns (LPS, MDP, and 5{\textquoteright}-ppp-dsRNA), and profile the transcriptomes at three time points. Mapping expression quantitative trait loci (eQTL), we identify 417 response eQTLs (reQTLs) with varying effects between conditions. We characterize the dynamics of genetic regulation on early and late immune response and observe an enrichment of reQTLs in distal cis-regulatory elements. In addition, reQTLs are enriched for recent positive selection with an evolutionary trend towards enhanced immune response. Finally, we uncover reQTL effects in multiple GWAS loci and show a stronger enrichment for response than constant eQTLs in GWAS signals of several autoimmune diseases. This demonstrates the importance of infectious stimuli in modifying genetic predisposition to disease.Insight into the genetic influence on the immune response is important for the understanding of interindividual variability in human pathologies. Here, the authors generate transcriptome data from human blood monocytes stimulated with various immune stimuli and provide a time-resolved response eQTL map.</p>},
	keywords = {Acetylmuramyl-Alanyl-Isoglutamine, Adjuvants, Immunologic, Adolescent, Adult, Autoimmune Diseases, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Genetic Predisposition to Disease, Healthy Volunteers, Humans, Indicators and Reagents, Lipids, Lipopolysaccharides, Male, Monocytes, Quantitative Trait Loci, Regulatory Sequences, Nucleic Acid, RNA, Double-Stranded, RNA, Messenger, Young Adult},
	issn = {2041-1723},
	doi = {10.1038/s41467-017-00366-1},
	author = {Kim-Hellmuth, Sarah and Bechheim, Matthias and P{\"u}tz, Benno and Mohammadi, Pejman and N{\'e}d{\'e}lec, Yohann and Giangreco, Nicholas and Becker, Jessica and Kaiser, Vera and Fricker, Nadine and Beier, Esther and Boor, Peter and Castel, Stephane E and N{\"o}then, Markus M and Barreiro, Luis B and Pickrell, Joseph K and M{\"u}ller-Myhsok, Bertram and Lappalainen, Tuuli and Schumacher, Johannes and Hornung, Veit}
}
