The impact of rare and low-frequency genetic variants in common disease

L Bomba, K Walter, N Soranzo - Genome biology, 2017 - Springer
Despite thousands of genetic loci identified to date, a large proportion of genetic variation
predisposing to complex disease and traits remains unaccounted for. Advances in …

Rare-variant association analysis: study designs and statistical tests

S Lee, GR Abecasis, M Boehnke, X Lin - The American Journal of Human …, 2014 - cell.com
Despite the extensive discovery of trait-and disease-associated common variants, much of
the genetic contribution to complex traits remains unexplained. Rare variants can explain …

Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

MA Nalls, N Pankratz, CM Lill, CB Do, DG Hernandez… - Nature …, 2014 - nature.com
We conducted a meta-analysis of Parkinson's disease genome-wide association studies
using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty …

Comparison and integration of deleteriousness prediction methods for nonsynonymous SNVs in whole exome sequencing studies

C Dong, P Wei, X Jian, R Gibbs… - Human molecular …, 2015 - academic.oup.com
Accurate deleteriousness prediction for nonsynonymous variants is crucial for distinguishing
pathogenic mutations from background polymorphisms in whole exome sequencing (WES) …

Whole‐genome sequencing identifies EN1 as a determinant of bone density and fracture

HF Zheng, V Forgetta, YH Hsu, K Estrada… - Nature, 2015 - nature.com
The extent to which low‐frequency (minor allele frequency (MAF) between 1–5%) and rare
(MAF≤ 1%) variants contribute to complex traits and disease in the general population is …

Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index

J Yang, A Bakshi, Z Zhu, G Hemani, AAE Vinkhuyzen… - Nature …, 2015 - nature.com
We propose a method (GREML-LDMS) to estimate heritability for human complex traits in
unrelated individuals using whole-genome sequencing data. We demonstrate using …

minimac2: faster genotype imputation

C Fuchsberger, GR Abecasis, DA Hinds - Bioinformatics, 2014 - academic.oup.com
Genotype imputation is a key step in the analysis of genome-wide association studies.
Upcoming very large reference panels, such as those from The 1000 Genomes Project and …

Cohort Profile: The Framingham Heart Study (FHS): overview of milestones in cardiovascular epidemiology

CW Tsao, RS Vasan - International journal of epidemiology, 2015 - academic.oup.com
Abstract The Framingham Heart Study (FHS) has conducted seminal research defining
cardiovascular disease (CVD) risk factors and fundamentally shaping public health …

In silico prediction of splice-altering single nucleotide variants in the human genome

X Jian, E Boerwinkle, X Liu - Nucleic acids research, 2014 - academic.oup.com
In silico tools have been developed to predict variants that may have an impact on pre-
mRNA splicing. The major limitation of the application of these tools to basic research and …

Searching for missing heritability: designing rare variant association studies

O Zuk, SF Schaffner, K Samocha… - Proceedings of the …, 2014 - National Acad Sciences
Genetic studies have revealed thousands of loci predisposing to hundreds of human
diseases and traits, revealing important biological pathways and defining novel therapeutic …