Expressive

rs113817010 - RBBP5 - DSTYK

Magnitude 2.0 · 5 studies on file

Reported associations

  • A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology - Nature communications (2023) · Akbari P, Vuckovic D, Stefanucci L, Jiang T, Kundu K, Kreuzhuber R, Bao EL, Collins JH, Downes K, Grassi L, Guerrero JA, Kaptoge S, Knight JC, Meacham S, Sambrook J, Seyres D, Stegle O, Verboon JM, Walter K, Watkins NA, Danesh J, Roberts DJ, Di Angelantonio E, Sankaran VG, Frontini M, Burgess S, Kuijpers T, Peters JE, Butterworth AS, Ouwehand WH, Soranzo N, Astle WJ · PubMed 37596262

    ABSTRACT: Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes-including cell-type specific measures of granularity, nucleic acid content and reactivity-in 41,515 participants in the INTERVAL study. We identify 2172 distinct variant-trait associations, including associations near genes coding for proteins in organelles implicated in inflammatory and thrombotic diseases. By integrating with epigenetic data we show that many intracellular structures are likely to be determined in immature precursor cells. By integrating

  • Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain - Nature communications (2022) · Fan CC, Loughnan R, Makowski C, Pecheva D, Chen CH, Hagler DJ, Thompson WK, Parker N, van der Meer D, Frei O, Andreassen OA, Dale AM · PubMed 35505052

    ABSTRACT: The molecular determinants of tissue composition of the human brain remain largely unknown. Recent genome-wide association studies (GWAS) on this topic have had limited success due to methodological constraints. Here, we apply advanced whole-brain analyses on multi-shell diffusion imaging data and multivariate GWAS to two large scale imaging genetic datasets (UK Biobank and the Adolescent Brain Cognitive Development study) to identify and validate genetic association signals. We discover 503 unique genetic loci that have impact on multiple regions of human brain. Among them, more than 79% are validated in either of two large-scale independent imaging datasets. Key molecular pathways involved in axonal growth, astrocyte-mediated neuroinflammation, and synaptogenesis during develop

  • Boosting Schizophrenia Genetics by Utilizing Genetic Overlap With Brain Morphology. - Biological psychiatry (2022) · van der Meer D, Shadrin AA, O'Connell K, Bettella F, Djurovic S, Wolfers T, Alnæs D, Agartz I, Smeland OB, Melle I, Sánchez JM, Linden DEJ, Dale AM, Westlye LT, Andreassen OA, Frei O, Kaufmann T · PubMed 35164939

    Schizophrenia is a complex polygenic disorder with subtle, distributed abnormalities in brain morphology. There are indications of shared genetic architecture between schizophrenia and brain measures despite low genetic correlations. Through the use of analytical methods that allow for mixed directions of effects, this overlap may be leveraged to improve our understanding of underlying mechanisms of schizophrenia and enrich polygenic risk prediction outcome. We ran a multivariate genome-wide analysis of 175 brain morphology measures using data from 33,735 participants of the UK Biobank and analyzed the results in a conditional false discovery rate together with schizophrenia genome-wide association study summary statistics of the Psychiatric Genomics Consortium (PGC) Wave 3. We subsequentl

  • Vertex-wise multivariate genome-wide association study identifies 780 unique genetic loci associated with cortical morphology - NeuroImage (2022) · Shadrin AA, Kaufmann T, van der Meer D, Palmer CE, Makowski C, Loughnan R, Jernigan TL, Seibert TM, Hagler DJ, Smeland OB, Motazedi E, Chu Y, Lin A, Cheng W, Hindley G, Thompson WK, Fan CC, Holland D, Westlye LT, Frei O, Andreassen OA, Dale AM · PubMed 34560273

    ABSTRACT: Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we extended the Multivariate Omnibus Statistical Test (MOSTest) and applied it to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) cortical measures from N=35,657 participants in the UK Biobank. We identified 695 loci for cortical surface area and 539 for cortical thickness, in total 780 unique genetic loci associated with cortical morphology robustly replicated in 8,060 children of mixed ethnicity from the Adolescent Brain Cognitive Development (ABCD) Study®. This reflects more than 8-fold increase in genetic discovery at no cost to generalizability compared to the commo

  • Understanding the genetic determinants of the brain with MOSTest - Nature communications (2020) · van der Meer D, Frei O, Kaufmann T, Shadrin AA, Devor A, Smeland OB, Thompson WK, Fan CC, Holland D, Westlye LT, Andreassen OA, Dale AM · PubMed 32665545

    ABSTRACT: Regional brain morphology has a complex genetic architecture, consisting of many common polymorphisms with small individual effects. This has proven challenging for genome-wide association studies (GWAS). Due to the distributed nature of genetic signal across brain regions, multivariate analysis of regional measures may enhance discovery of genetic variants. Current multivariate approaches to GWAS are ill-suited for complex, large-scale data of this kind. Here, we introduce the Multivariate Omnibus Statistical Test (MOSTest), with an efficient computational design enabling rapid and reliable inference, and apply it to 171 regional brain morphology measures from 26,502 UK Biobank participants. At the conventional genome-wide significance threshold of α = 5 × 10−8, MOS

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