Population- and individual-specific regulatory variation in Sardinia

Francesco Cucca, Stephen Montgomery and colleagues identify regulatory variants that influence gene expression and splicing using whole-genome and transcriptome sequence data from 624 Sardinians. They find a high frequency of splicing and expression quantitative trait loci near genes involved in mal...

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Vydáno v:	Nature genetics Ročník 49; číslo 5; s. 700 - 707
Hlavní autoři:	Pala, Mauro, Zappala, Zachary, Marongiu, Mara, Li, Xin, Davis, Joe R, Cusano, Roberto, Crobu, Francesca, Kukurba, Kimberly R, Gloudemans, Michael J, Reinier, Frederic, Berutti, Riccardo, Piras, Maria G, Mulas, Antonella, Zoledziewska, Magdalena, Marongiu, Michele, Sorokin, Elena P, Hess, Gaelen T, Smith, Kevin S, Busonero, Fabio, Maschio, Andrea, Steri, Maristella, Sidore, Carlo, Sanna, Serena, Fiorillo, Edoardo, Bassik, Michael C, Sawcer, Stephen J, Battle, Alexis, Novembre, John, Jones, Chris, Angius, Andrea, Abecasis, Gonçalo R, Schlessinger, David, Cucca, Francesco, Montgomery, Stephen B
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.05.2017 Nature Publishing Group
Témata:	38 38/91 45 45/23 45/43 631/208/191/2018 631/208/205/2138 631/208/212/2019 631/208/457 Agriculture Alternative Splicing Animal Genetics and Genomics Bioinformatics Biomedicine Blood Cancer Research Chromosome Mapping Epidemiology Family Health Female Gene expression Gene Expression Profiling - methods Gene Function Gene mapping Genes Genetic Predisposition to Disease - genetics Genetic Variation Genetics Genetics, Population Genome-Wide Association Study - methods Genomes Genotype Human Genetics Humans Italy Male Multiple sclerosis Outliers (statistics) Polymorphism, Single Nucleotide Population Population genetics Proteins Quantitative trait loci Quantitative Trait Loci - genetics Splicing Studies Transcription Initiation Site United States > US California
ISSN:	1061-4036, 1546-1718, 1546-1718
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Shrnutí:	Francesco Cucca, Stephen Montgomery and colleagues identify regulatory variants that influence gene expression and splicing using whole-genome and transcriptome sequence data from 624 Sardinians. They find a high frequency of splicing and expression quantitative trait loci near genes involved in malarial resistance and multiple sclerosis. Genetic studies of complex traits have mainly identified associations with noncoding variants. To further determine the contribution of regulatory variation, we combined whole-genome and transcriptome data for 624 individuals from Sardinia to identify common and rare variants that influence gene expression and splicing. We identified 21,183 expression quantitative trait loci (eQTLs) and 6,768 splicing quantitative trait loci (sQTLs), including 619 new QTLs. We identified high-frequency QTLs and found evidence of selection near genes involved in malarial resistance and increased multiple sclerosis risk, reflecting the epidemiological history of Sardinia. Using family relationships, we identified 809 segregating expression outliers (median z score of 2.97), averaging 13.3 genes per individual. Outlier genes were enriched for proximal rare variants, providing a new approach to study large-effect regulatory variants and their relevance to traits. Our results provide insight into the effects of regulatory variants and their relationship to population history and individual genetic risk.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Equal contributions statement co-first authors These authors contributed equally: Mauro Pala, Zachary Zappala co-senior authors
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/ng.3840