A brief history of human disease genetics

M Claussnitzer, JH Cho, R Collins, NJ Cox… - Nature, 2020 - nature.com
A primary goal of human genetics is to identify DNA sequence variants that influence
biomedical traits, particularly those related to the onset and progression of human disease …

Genetics of mitochondrial diseases: Identifying mutations to help diagnosis

SL Stenton, H Prokisch - EBioMedicine, 2020 - thelancet.com
Mitochondrial diseases are amongst the most genetically and phenotypically diverse groups
of inherited diseases. The vast phenotypic overlap with other disease entities together with …

Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions

AC Fahed, M Wang, JR Homburger, AP Patel… - Nature …, 2020 - nature.com
Genetic variation can predispose to disease both through (i) monogenic risk variants that
disrupt a physiologic pathway with large effect on disease and (ii) polygenic risk that …

Whole-genome sequencing of patients with rare diseases in a national health system

E Turro, WJ Astle, K Megy, S Gräf, D Greene… - Nature, 2020 - nature.com
Most patients with rare diseases do not receive a molecular diagnosis and the aetiological
variants and causative genes for more than half such disorders remain to be discovered …

The polygenic and monogenic basis of blood traits and diseases

D Vuckovic, EL Bao, P Akbari, CA Lareau, A Mousas… - Cell, 2020 - cell.com
Blood cells play essential roles in human health, underpinning physiological processes
such as immunity, oxygen transport, and clotting, which when perturbed cause a significant …

Genetic interleukin 6 signaling deficiency attenuates cardiovascular risk in clonal hematopoiesis

AG Bick, JP Pirruccello, GK Griffin, N Gupta, S Gabriel… - Circulation, 2020 - Am Heart Assoc
Background: Clonal hematopoiesis of indeterminate potential (CHIP) refers to clonal
expansion of hematopoietic stem cells attributable to acquired leukemic mutations in genes …

A resource-efficient tool for mixed model association analysis of large-scale data

L Jiang, Z Zheng, T Qi, KE Kemper, NR Wray… - Nature …, 2019 - nature.com
The genome-wide association study (GWAS) has been widely used as an experimental
design to detect associations between genetic variants and a phenotype. Two major …

Dynamic incorporation of multiple in silico functional annotations empowers rare variant association analysis of large whole-genome sequencing studies at scale

X Li, Z Li, H Zhou, SM Gaynor, Y Liu, H Chen, R Sun… - Nature …, 2020 - nature.com
Large-scale whole-genome sequencing studies have enabled the analysis of rare variants
(RVs) associated with complex phenotypes. Commonly used RV association tests have …

Dnmt3a-mutated clonal hematopoiesis promotes osteoporosis

PG Kim, A Niroula, V Shkolnik, M McConkey… - Journal of Experimental …, 2021 - rupress.org
Osteoporosis is caused by an imbalance of osteoclasts and osteoblasts, occurring in close
proximity to hematopoietic cells in the bone marrow. Recurrent somatic mutations that lead …

Functionally informed fine-mapping and polygenic localization of complex trait heritability

O Weissbrod, F Hormozdiari, C Benner, R Cui… - Nature …, 2020 - nature.com
Fine-mapping aims to identify causal variants impacting complex traits. We propose
PolyFun, a computationally scalable framework to improve fine-mapping accuracy by …