Joseph B. Leader
Geisinger Health System
Publications 56
#1Claudia Gonzaga-Jauregui (Regeneron)H-Index: 7
#2Wenzhen Ge (Regeneron)
Last.Judith Altarejos (Regeneron)
view all 18 authors...
Lipodystrophies are a group of disorders characterized by absence or loss of adipose tissue and abnormal fat distribution, commonly accompanied by metabolic dysregulation. Although considered rare disorders, their prevalence in the general population is not well understood. We aimed to evaluate the clinical and genetic prevalence of lipodystrophy disorders in a large clinical care cohort. We interrogated the electronic health record (EHR) information of >1.3 million adults from the Geisinger Hea...
#1Juan M. Banda (Stanford University)H-Index: 14
#2Ashish Sarraju (Cardiovascular Institute of the South)H-Index: 4
Last.Joshua W. Knowles (Cardiovascular Institute of the South)H-Index: 42
view all 18 authors...
Familial hypercholesterolemia (FH) is an underdiagnosed dominant genetic condition affecting approximately 0.4% of the population and has up to a 20-fold increased risk of coronary artery disease if untreated. Simple screening strategies have false positive rates greater than 95%. As part of the FH Foundation′s FIND FH initiative, we developed a classifier to identify potential FH patients using electronic health record (EHR) data at Stanford Health Care. We trained a random forest classifier us...
3 CitationsSource
#1Eric D. CarruthH-Index: 5
Last.Christopher M. HaggertyH-Index: 17
view all 17 authors...
Background - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with variants in desmosome genes. Secondary findings of pathogenic/likely pathogenic variants, primarily loss-of-fu...
#1Gregory J. Wehner (UK: University of Kentucky)H-Index: 7
#2Linyuan JingH-Index: 9
Last.Brandon K. FornwaltH-Index: 15
view all 14 authors...
4 CitationsSource
#2Scott M. Damrauer (UPenn: University of Pennsylvania)H-Index: 17
Last.Zoltan Arany (UPenn: University of Pennsylvania)H-Index: 36
view all 39 authors...
Background: Truncating variants in the Titin gene (TTNtvs) are common in individuals with idiopathic dilated cardiomyopathy (DCM). However, a comprehensive genomics-first evaluation of the impact o...
2 CitationsSource
Last.David J. CareyH-Index: 52
view all 11 authors...
#1Jason FlannickH-Index: 32
#2Josep M. MercaderH-Index: 26
Last.Michael Boehnke (UM: University of Michigan)H-Index: 122
view all 164 authors...
Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, ...
12 CitationsSource
#1Gina M. Peloso (BU: Boston University)H-Index: 43
#2Akihiro Nomura (Kanazawa University)H-Index: 14
Last.Sekar Kathiresan (Broad Institute)H-Index: 106
view all 26 authors...
GMP is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number K01HL125751. AN was supported by the Yoshida Scholarship Foundation. AK is supported by an institutional grant from the Broad Institute of MIT and Harvard (BroadIgnite), a K08 from the National Human Genome Research Institute (K08HG010155), and a Junior Faculty Award from the National Lipid Association. SK is supported by a research scholar award from the Massachusetts Genera...
2 CitationsSource
#1Gina M. PelosoH-Index: 43
#2Akihiro NomuraH-Index: 14
Last.Sekar KathiresanH-Index: 106
view all 26 authors...
Background: Familial hypobetalipoproteinemia (FHBL) is a genetic disorder caused by rare protein-truncating variants (PTV) in the gene encoding apolipoprotein B (APOB), the major protein component of low-density and triglyceride-rich lipoprotein particles. Whether heterozygous APOB deficiency is associated with decreased risk for coronary heart disease (CHD) is uncertain. We combined family-based and large scale gene-sequencing to characterize the association of rare PTVs in APOB with circulatin...
2 Citations
#2Ioanna Tachmazidou (GSK: GlaxoSmithKline)H-Index: 1
Last.Aris BarasH-Index: 14
view all 49 authors...
SUMMARY The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world. Here we describe the first tranche of large-scale exome sequence data for 49,960 study participants, revealing approximately 4 million coding variants (of which ~98.4% have frequency 10-fold increase compared to imputed sequence for the same participants. Nearly all genes (>97%) had ≥1 predicted loss of function carrier,...
19 CitationsSource