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Genetic studies of body mass index yield new insights for obesity biology
TLDR
A genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals provide strong support for a role of the central nervous system in obesity susceptibility.
Human Hypertension Caused by Mutations in WNK Kinases
TLDR
Two genes causing pseudohypoaldosteronism type II, a Mendelian trait featuring hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion are identified.
Autoantibodies against type I IFNs in patients with life-threatening COVID-19
TLDR
A means by which individuals at highest risk of life-threatening COVID-19 can be identified is identified, and the hypothesis that neutralizing auto-Abs against type I IFNs may underlie critical CO VID-19 is tested.
K+ Channel Mutations in Adrenal Aldosterone-Producing Adenomas and Hereditary Hypertension
TLDR
An inherited KCNJ5 mutation that produces increased Na+ conductance in a Mendelian form of severe aldosteronism and massive bilateral adrenal hyperplasia is identified, explaining pathogenesis in a subset of patients with severe hypertension and implicate loss of K+ channel selectivity in constitutive cell proliferation and hormone production.
Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma
TLDR
Crystal structures, biochemical and functional studies of RAC1P29S showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration, raising the possibility that pharmacological inhibition of downstream effector of Rac1 signaling could be of therapeutic benefit.
De novo mutations revealed by whole-exome sequencing are strongly associated with autism
TLDR
It is shown, using whole-exome sequencing of 928 individuals, including 200 phenotypically discordant sibling pairs, that highly disruptive (nonsense and splice-site) de novo mutations in brain-expressed genes are associated with autism spectrum disorders and carry large effects.
Mutations in Kelch-like 3 and Cullin 3 cause hypertension and electrolyte abnormalities
TLDR
The utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation is demonstrated, and a fundamental role for KLHL3 and CUL3 in blood pressure, K+ and pH homeostasis is established.
New genetic loci link adipose and insulin biology to body fat distribution
TLDR
A genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Gitelman's variant of Barter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na–Cl cotransporter
TLDR
It is speculated that a wide variety of non-conservative mutations, consistent with loss of function alleles, in affected subjects lead to reduced sodium chloride reabsorption in the more common heterozygotes, potentially protecting against development of hypertension.
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