References of "Johnson, Robert"
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See detailNovel genetic loci associated with hippocampal volume.
Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda et al

in Nature Communications (2017), 8

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are ... [more ▼]

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness. [less ▲]

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See detailNovel genetic loci underlying human intracranial volume identified through genome-wide association.
Adams, Hieab H. H.; Hibar, Derrek P.; Chouraki, Vincent et al

in Nature Neuroscience (2016), 19(12), 1569-1582

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely ... [more ▼]

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rhogenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits. [less ▲]

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See detailCommon genetic variants influence human subcortical brain structures.
Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E. et al

in Nature (2015), 520(7546), 224-9

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and ... [more ▼]

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. [less ▲]

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See detailEvidence of involvement of yeast proliferating cell nuclear antigen in DNA mismatch repair
Johnson, Robert; Kovvali, G.; Guzder, Sami et al

in Journal of Biological Chemistry (1996), 271(45), 27897-90

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See detailHow should zoster trials be conducted?
Wood, M. J.; Balfour, Hank; Beutner, Karl et al

in Journal of Antimicrobial Chemotherapy (1995), 36(6), 1089-1101

In 1994, an international group of interested clinicians and biostatisticians met to discuss the design of clinical trials in herpes tester. They agreed that trials in herpes tester should have ... [more ▼]

In 1994, an international group of interested clinicians and biostatisticians met to discuss the design of clinical trials in herpes tester. They agreed that trials in herpes tester should have prospectively agreed definitions of all outcome measures and plans for data analysis. In immunocompetent individuals, in whom pain is the major outcome measure, trials should only include patients over the age of 50 years, and for those recruited within 72 fi of rash onset, should be designed to demonstrate superiority of any new therapy over existing antivirals. The primary endpoint should be time to cessation of pain for at least 4 weeks and, for the purposes of statistical analysis of its duration, the pain associated with herpes tester ought to be considered as a continuum. All other variables, including the incidence of post-herpetic neuralgia and effects upon quality of life should be considered as secondary end-points. Evaluation of treatment effects on primary endpoints should be based upon an intent-to-treat (ITT) analysis and subgroup analysis should be used only to support the findings of the ITT analysis. These elements of good study design should be borne in mind in the evaluation of current and future trails of antiviral drugs in herpes zoster. [less ▲]

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