Identification of context-dependent expression quantitative trait loci in whole blood.
Daria V ZhernakovaPatrick DeelenMartijn VermaatMaarten van ItersonMichiel van GalenWibowo ArindrartoPeter van 't HofHailiang MeiFreerk van DijkHarm-Jan WestraMarc Jan BonderJeroen van RooijMarijn VerkerkP Mila JhamaiMatthijs MoedSzymon M KielbasaJan BotIrene NoorenRené PoolJenny van DongenJouke J HottengaCoen D A StehouwerCarla J H van der KallenCasper G SchalkwijkAlexandra ZhernakovaYang LiEttje F TigchelaarNiek de KleinMarian BeekmanJoris DeelenDiana van HeemstLeonard H van den BergAlbert HofmanAndré G UitterlindenMarleen M J van GreevenbroekJan H VeldinkDorret I BoomsmaCornelia M van DuijnCisca WijmengaP Eline SlagboomMorris A SwertzAaron IsaacsJoyce B J van MeursRick JansenBastiaan T HeijmansPeter A C 't HoenLude FrankePublished in: Nature genetics (2016)
Genetic risk factors often localize to noncoding regions of the genome with unknown effects on disease etiology. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying these genetic associations. Knowledge of the context that determines the nature and strength of eQTLs may help identify cell types relevant to pathophysiology and the regulatory networks underlying disease. Here we generated peripheral blood RNA-seq data from 2,116 unrelated individuals and systematically identified context-dependent eQTLs using a hypothesis-free strategy that does not require previous knowledge of the identity of the modifiers. Of the 23,060 significant cis-regulated genes (false discovery rate (FDR) ≤ 0.05), 2,743 (12%) showed context-dependent eQTL effects. The majority of these effects were influenced by cell type composition. A set of 145 cis-eQTLs depended on type I interferon signaling. Others were modulated by specific transcription factors binding to the eQTL SNPs.