Exploring the impact of ultra-rare variants across diseases and traits

Dnr:

SNIC 2017/7-147

Type:

SNAC Small

Principal Investigator:

Andrea Ganna

Affiliation:

Karolinska Institutet

Start Date:

2017-09-11

End Date:

2018-10-01

Primary Classification:

10609: Genetik (medicinsk under 30107 och lantbruksvetenskaplig under 40402)

Webpage:

Allocation

Abstract

Private disruptive mutations (causing protein truncation, loss of function or triggering nonsense mediated decay) in highly constrained (HC) genes play a pivotal role in Mendelian disorders [PMID: 25086666], but they have been also associated in relatively more common neurodevelopmental disorders such as autism [PMID: 25961944], intellectual disability [PMID: 24896178] and schizophrenia (Giulio Genovese, unpublished). However, little is known about the impact of such mutations on non-neurodevelopmental common diseases. We will focus on three types of analysis: 1) Association between private disruptive mutations in ECG and ~ 30 common diseases defined via registries (see below a initial list based on Finnish registries) 2) Unbiased association between private disruptive mutations in ECG and main ICD category (e.g. D23) 3) Association between private disruptive mutations in ECG and overall burden of diseases (e.g. number of visits to the hospital)