Publications related to Genome-wide complex trait analysis

DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin study

Background Puberty is a highly heritable and variable trait, with environmental factors having a role in its eventual timing and development. Early and late pubertal onset are both associated with various diseases developing later in life, and epigenetic c ...

BMC2023

Identifying genetic and dietary modulators of metabolic disorders using systems genetics

Xiaoxu Li

Long-term consumption of lipid-rich foods can contribute to common metabolic diseases and systemic low-grade inflammation. However, dietary responses and the development of non-communicable diseases are shaped by genetic factors and gene-by-environment int ...

EPFL2023

A Phylogeny-aware GWAS Framework to Correct for Heritable Pathogen Effects on Infectious Disease Traits

Jacques Fellay, Christian Axel Wandall Thorball

Infectious diseases are particularly challenging for genome-wide association studies (GWAS) because genetic effects from two organisms (pathogen and host) can influence a trait. Traditional GWAS assume individual samples are independent observations. Howev ...

OXFORD UNIV PRESS2022

The genetic architecture of complex human traits at the dawn of genomic medicine

Olivier Noël Marie Naret

The focus of the work presented in this thesis is the exploration of the genetic architecture of complex human traits - at the dawn of genomic medicine. The underlying mechanisms explaining the enormously polygenic nature of most human complex traits are ...

EPFL2021

A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response

Jacques Fellay, John Wilson, Yang Luo, Xinyi Li

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response. ...

NATURE PORTFOLIO2021

A platform for experimental precision medicine: The extended BXD mouse family

Johan Auwerx, Evan Graehl Williams

The challenge of precision medicine is to model complex interactions among DNA variants, phenotypes, development, environments, and treatments. We address this challenge by expanding the BXD family of mice to 140 fully isogenic strains, creating a uniquely ...

CELL PRESS2021

A fully joint Bayesian quantitative trait locus mapping of human protein abundance in plasma

Anthony Christopher Davison, Hélène Ruffieux, Jörg Hager, Radu Popescu

Molecular quantitative trait locus (QTL) analyses are increasingly popular to explore the genetic architecture of complex traits, but existing studies do not leverage shared regulatory patterns and suffer from a large multiplicity burden, which hampers the ...

PUBLIC LIBRARY SCIENCE2020

Genetic spectrum of retinal dystrophies in Tunisia

Imen Habibi

We report the molecular basis of the largest Tunisian cohort with inherited retinal dystrophies (IRD) reported to date, identify disease-causing pathogenic variants and describe genotype-phenotype correlations. A subset of 26 families from a cohort of 73 f ...

Nature Research2020

Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB)

Imen Habibi

Mutations in BEST1 cause several phenotypes including autosomal dominant (AD) Best vitelliform macular dystrophy type 2 (BVMD), AD vitreo-retino-choroidopathy (ADVIRC), and retinitis pigmentosa-50 (RP50). A rare subtype of Bestrophinopathy exists with bial ...

2019

Large-scale variational inference for Bayesian joint regression modelling of high-dimensional genetic data

Hélène Ruffieux

Genetic association studies have become increasingly important in understanding the molecular bases of complex human traits. The specific analysis of intermediate molecular traits, via quantitative trait locus (QTL) studies, has recently received much atte ...

EPFL2019

Systems genetics approaches to probe gene function

Hao Li

Genes are the functional units of heredity. However, the functions of many genes remain unknown, which impedes the understanding of the underlying mechanism of complex traits and diseases. Systems genetics approaches try to understand the complexity underl ...

EPFL2019

Novel PDE6B Mutation Presenting with Retinitis Pigmentosa - A Case Series of Three Patients

Imen Habibi

Background Retinitis pigmentosa (RP) affects 2.5 million people worldwide. Increased identification of causative gene defects and the increasing possibility of treatment necessitates better knowledge of phenotype-genotype correlations to help identify pati ...

2019

Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T Cell Decline and Per-Parasite Pathogenicity

Jacques Fellay, Gabriel Leventhal

Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as" per-parasite pathogen ...

Oxford University Press2018

The phenotypic impact of naturally occurring genetic and molecular mitochondrial variation in a Drosophila Genetic Reference Population

Roel Paulus Josephus Bevers

Genome-wide association (GWA) studies aim to dissect the relationship between genotype and phenotype. So far, the focus has been on nuclear genetic determinants as variation in the mitochondrial genome is often low in the study cohorts. Despite this observ ...

EPFL2018

Inferring the age and strength of mutations evolving under positive selection

Nicky Louise Ormond

A fundamental goal of population genetics is to determine and quantify the interplay of mutation, natural selection, genetic drift and migration in shaping allelic frequency changes that underpin evolution-ary change. In this dissertation, I present comput ...

EPFL2017

The Drosophila gut response to infection : a systems approach

Maroun Bou Sleiman

Genetic, physiological, and biochemical studies have successfully ascribed functions to genes in diverse processes. However, the majority of our knowledge in biology is qualitative in nature and is usually based on classical screens, where large effects on ...

EPFL2016

Ecological strategies in stable and disturbed environments depend on species specialisation

Séverine Vuilleumier Varisco

Ecological strategies are integral to understanding species survival in different environments. However, how habitat specialisation is involved in such strategies is not fully understood, particularly in heterogeneous and disturbed environments. Here, we s ...

2016

Inferring the age of a fixed beneficial allele

Jeffrey David Jensen, Matthieu Foll, Susanne Petra Pfeifer, Nicky Louise Ormond, Gregory Bruce Ewing

Estimating the age and strength of beneficial alleles is central to understanding how adaptation proceeds in response to changing environmental conditions. Several haplotype-based estimators exist for inferring the age of segregating beneficial mutations. ...

Wiley-Blackwell2016

The Convergence of Systems and Reductionist Approaches in Complex Trait Analysis

Johan Auwerx, Evan Graehl Williams

Research into the genetic and environmental factors behind complex trait variation has traditionally been segregated into distinct scientific camps. The reductionist approach aims to decrypt phenotypic variability bit by bit, founded on the underlying hypo ...

2015

Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load

Jacques Fellay, Amalio Telenti, Istvan Bartha, Paul Jack Mc Laren

Previous genome-wide association studies (GWAS) of HIV-1-infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. ...

National Academy of Sciences2015