Recombinant Haplotypes Narrow the ARMS2/HTRA1 Association Signal for Age-Related Macular Degeneration

The authors thank Paul N. Baird (Ocular Genetics Unit, Centre for Eye Research, Australia) for critically reading the manuscript. The work was funded in part by grants from the German Federal Ministry of Education and Research (BMBF 01ER1206 and 01ER1507) to I.M.H., by the institutional budget for Research and Teaching from the Freestate of Bavaria and the German Research Foundation (WE 1259/19-2) to BHFW.Peer reviewedPublisher PD

A transcriptome-wide association study based on 27 tissues identifies 106 genes potentially relevant for disease pathology in age-related macular degeneration

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Genome Sequence of the Pea Aphid \u3ci\u3eAcyrthosiphon pisum\u3c/i\u3e

Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems

Investigating the modulation of genetic effects on late AMD by age and sex : Lessons learned and two additional loci

Funding: The authors gratefully acknowledge the excellent International Age-related Macular Degeneration Genomics Consortium (IAMDGC), (http://amdgenetics.org/). This analyses are supported by grants from the German Federal Ministry of Education and Research (BMBF 01ER1206, BMBF 01ER1507 to IMH, and BMBF 01GP1308) to JL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies

Objective: Tourette’s syndrome is polygenic and highly heritable. Genome-wide association study (GWAS) approaches are useful for interrogating the genetic architecture and determinants of Tourette’s syndrome and other tic disorders. The authors conducted a GWAS meta-analysis and probed aggregated Tourette’s syndrome polygenic risk to test whether Tourette’s and related tic disorders have an underlying shared genetic etiology and whether Tourette’s polygenic risk scores correlate with worst-ever tic severity and may represent a potential predictor of disease severity. Methods: GWAS meta-analysis, gene-based association, and genetic enrichment analyses were conducted in 4,819 Tourette’s syndrome case subjects and 9,488 control subjects. Replication of top loci was conducted in an independent population-based sample (706 case subjects, 6,068 control subjects). Relationships between Tourette’s polygenic risk scores (PRSs), other tic disorders, ascertainment, and tic severity were examined. Results: GWAS and gene-based analyses identified one genome-wide significant locus within FLT3 on chromosome 13, rs2504235, although this association was not replicated in the population-based sample. Genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette’s syndrome heritability. Tourette’s-associated genes were significantly preferentially expressed in dorsolateral prefrontal cortex. Tourette’s PRS significantly predicted both Tourette’s syndrome and tic spectrum disorders status in the population-based sample. Tourette’s PRS also significantly correlated with worst-ever tic severity and was higher in case subjects with a family history of tics than in simplex case subjects. Conclusions: Modulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette’s syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette’s syndrome and other tic disorders in future diagnostic schemata. Tourette’s PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity

Y chromosome mosaicism is associated with age-related macular degeneration

Acknowledgements The authors thank Sudha K. Iyengar, Rob Igo and Alberto H. Santana (Case Western Reserve University, Cleveland, Ohio, USA) as well as the IAMDGC (http://eaglep.case.edu/iamdgc_web/) for providing the raw probe intensities. We are also grateful to valuable comments to the manuscript from Michael Gorin (Jules Stein Eye Institute, Los Angeles, CA, USA). The list of consortium members reflects the author list of the previous publication by Fritsche et al. 2016 [9], which is listed in the Supplement. Funding The work was funded, in parts by a grant from the German Research Foundation (GR 5065/1-1 to FG) and institutional funds of the Institute of Human Genetics, University of Regensburg (TG77 to BHFW). Genotyping was conducted as part of the IAMDGC exome-chip project supported by CIDR (contract number HHSN268201200008I) and funded by EY022310 (to Jonathan L. Haines, Case Western Reserve University, Cleveland) and 1 × 01HG006934-01 (to Gonçalo R. Abecasis, University of Michigan, Department of Biostatistics). The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.Peer reviewedPublisher PD

Hubert Puchberger: Nijema snaga znaka

Prijevod teksta o značenju i važnosti riječi u liturgiji nakon II. vatikanskog sabora

Pleiotropic Locus 15q24.1 Reveals a Gender-Specific Association with Neovascular but Not Atrophic Age-Related Macular Degeneration (AMD)

Funding This research was funded by the Deutsche Forschungsgemeinschaft (GR5065/1-1) and institutional funds (Titel 77). Acknowledgments All contributing sites and additional funding information for the IAMDGC data are acknowledged in this publication: Fritsche et al. (2016) Nature Genetics 48 134–143, (doi:10.1038/ng.3448); The International AMD Genomics consortium’s web page is: http://eaglep.case.edu/iamdgc_web/, and additional information is available on: http://csg.sph.umich.edu/abecasis/public/amd2015/. GERA data came from a grant, the Resource for Genetic Epidemiology Research in Adult Health and Aging (RC2 AG033067; Schaefer and Risch, PIs) awarded to the Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) and the UCSF Institute for Human Genetics. The RPGEH was supported by grants from the Robert Wood Johnson Foundation, the Wayne and Gladys Valley Foundation, the Ellison Medical Foundation, Kaiser Permanente Northern California, and the Kaiser Permanente National and Northern California Community Benefit Programs. The RPGEH and the Resource for Genetic Epidemiology Research in Adult Health and Aging are described in the following publication, Schaefer C, et al., The Kaiser Permanente Research Program on Genes, Environment and Health: Development of a Research Resource in a Multi-Ethnic Health Plan with Electronic Medical Records, In preparation, 2013. This research has been conducted using the UK Biobank Resource under Application Number 44862. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health (commonfund.nih.gov/GTEx). Additional funds were provided by the NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Donors were enrolled at Biospecimen Source Sites funded by NCI\Leidos Biomedical Research, Inc. subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute (10XS171), and Science Care, Inc. (X10S172). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to The Broad Institute, Inc. Biorepository operations were funded through a Leidos Biomedical Research, Inc. subcontract to Van Andel Research Institute (10ST1035). Additional data repository and project management were provided by Leidos Biomedical Research, Inc. (HHSN261200800001E). The Brain Bank was supported supplements to University of Miami grant DA006227. Statistical Methods development grants were made to the University of Geneva (MH090941 & MH101814), the University of Chicago (MH090951, MH090937, MH101825, & MH101820), the University of North Carolina—Chapel Hill (MH090936), North Carolina State University (MH101819), Harvard University (MH090948), Stanford University (MH101782), Washington University (MH101810), and to the University of Pennsylvania (MH101822). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000424.v8.p2.Peer reviewedPublisher PD