Den genetiska arkitekturen för kliniska kvantitativa karaktärer - En kartläggning av genetiska varianters betydelse för blodfetter och glykannivåer, samt komplexa sjukdomar som allergi och as

Tidsperiod: 2013-01-01 till 2015-12-31

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 2 700 000 SEK

Genome-wide association studies (GWAS) have provided insight into the genetic architecture of many chronic diseases, but translation of this knowledge into clinical practice has been limited. One reason for this is that the variants found only explain part of the expected heritability. The missing heritability could be due to rare genetic variants (SNPs, indels and CNVs) not detected by the GWAS. The aim of this study is to identify the full spectrum of genetic variation in genes from two clinically important metabolic pathways - circulating levels of blood lipids (classical lipids, fatty acids, phospholipids, sphingolipids) and N-glycans - in individuals with extreme phenotype values and by using next-generation DNA sequencing. Also, genes implicated in asthma and allergy will be studied. Novel statistical methods will be used to determine the role of rare and common genetic variants and their effects on the phenotype. Adjusting for environmental covariates will be used to study how the strength of genetic effects is affected by non-genetic factors. The functional consequence of the associated genetic variants in the target gene on pathway function will be studied using transcriptome sequencing and screening using in vitro expression assays. The project will provide a better understanding of the underlying genetic basis of clinically important quantitative traits and complex diseases, and thereby contribute to the utilisation of genetic information in medical practice.