Sökning: WFRF:(van Heemst D.) > Mendelian randomiza...
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000 | 06170naa a2201693 4500 | |
001 | oai:prod.swepub.kib.ki.se:141483442 | |
003 | SwePub | |
008 | 240829s2019 | |||||||||||000 ||eng| | |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1414834422 URI |
024 | 7 | a https://doi.org/10.1038/s41467-019-10936-02 DOI |
040 | a (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Porcu, E4 aut |
245 | 1 0 | a Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits |
264 | c 2019-07-24 | |
264 | 1 | b Springer Science and Business Media LLC,c 2019 |
520 | a Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs, indicating their potential involvement in regulation of gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and multiple gene expression traits as exposures, simultaneously. Applied to 43 human phenotypes, it uncovers 3,913 putatively causal gene–trait associations, 36% of which have no genome-wide significant SNP nearby in previous GWAS. Using independent association summary statistics, we find that the majority of these loci were missed by GWAS due to power issues. Noteworthy among these links is educational attainment-associated BSCL2, known to carry mutations leading to a Mendelian form of encephalopathy. We also find pleiotropic causal effects suggestive of mechanistic connections. TWMR better accounts for pleiotropy and has the potential to identify biological mechanisms underlying complex traits. | |
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710 | 2 | a Karolinska Institutet4 org |
773 | 0 | t Nature communicationsd : Springer Science and Business Media LLCg 10:1, s. 3300-q 10:1<3300-x 2041-1723 |
856 | 4 | u https://www.nature.com/articles/s41467-019-10936-0.pdf |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:141483442 |
856 | 4 8 | u https://doi.org/10.1038/s41467-019-10936-0 |
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