Expressive

rs12187568 - ADAMTS19-AS1

Magnitude 2.0 · 8 studies on file

Reported associations

  • The genetic architecture of human cortical folding - Science advances (2026) · van der Meer D, Kaufmann T, Shadrin AA, Makowski C, Frei O, Roelfs D, Monereo-Sánchez J, Linden DEJ, Rokicki J, Alnæs D, de Leeuw C, Thompson WK, Loughnan R, Fan CC, Westlye LT, Andreassen OA, Dale AM · PubMed 34910505

    ABSTRACT: The first genome-wide study of sulcal depth shows that it is highly genetically discoverable, associated with neurodevelopment. The folding of the human cerebral cortex is a highly genetically regulated process that allows for a much larger surface area to fit into the cranial vault and optimizes functional organization. Sulcal depth is a robust yet understudied measure of localized folding, previously associated with multiple neurodevelopmental disorders. Here, we report the first genome-wide association study of sulcal depth. Through the multivariate omnibus statistical test (MOSTest) applied to vertex-wise measures from 33,748 U.K. Biobank participants (mean age, 64.3 years; 52.0% female), we identified 856 genome-wide significant loci (P < 5 × 10−8). Comparisons with corti

  • Combining cross-sectional and longitudinal genomic approaches to identify determinants of cognitive and physical decline - Nature communications (2025) · Schoeler T, Pingault JB, Kutalik Z · PubMed 40374629

    ABSTRACT: Large-scale genomic studies focusing on the genetic contribution to human aging have mostly relied on cross-sectional data. With the release of longitudinally curated aging phenotypes by the UK Biobank (UKBB), it is now possible to study aging over time at genome-wide scale. In this work, we evaluated the suitability of competing models of change in realistic simulation settings, performed genome-wide association scans on simulation-validated measures of age-related deweekcline, and followed up with LD-score regression and Mendelian Randomization (MR) analyses. Focusing on global cognitive and physical function, we observed marked differences between baseline function (θ) and accelerated decline (Δ). Both outcomes showed distinct heritability levels (e.g., 31.38% versus 3.15%

  • Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study - Nature communications (2024) · Tissink EP, Shadrin AA, van der Meer D, Parker N, Hindley G, Roelfs D, Frei O, Fan CC, Nagel M, Nærland T, Budisteanu M, Djurovic S, Westlye LT, van den Heuvel MP, Posthuma D, Kaufmann T, Dale AM, Andreassen OA · PubMed 38531894

    ABSTRACT: Genetic pleiotropy is abundant across spatially distributed brain characteristics derived from one neuroimaging modality (e.g. structural, functional or diffusion magnetic resonance imaging [MRI]). A better understanding of pleiotropy across modalities could inform us on the integration of brain function, micro- and macrostructure. Here we show extensive genetic overlap across neuroimaging modalities at a locus and gene level in the UK Biobank (N = 34,029) and ABCD Study (N = 8607). When jointly analysing phenotypes derived from structural, functional and diffusion MRI in a genome-wide association study (GWAS) with the Multivariate Omnibus Statistical Test (MOSTest), we boost the discovery of loci and genes beyond previously identified effects for each modality individual

  • Genetic influences on brain and cognitive health and their interactions with cardiovascular conditions and depression - Nature communications (2024) · Zhukovsky P, Tio ES, Coughlan G, Bennett DA, Wang Y, Hohman TJ, Pizzagalli DA, Mulsant BH, Voineskos AN, Felsky D · PubMed 38890310

    ABSTRACT: Approximately 40% of dementia cases could be prevented or delayed by modifiable risk factors related to lifestyle and environment. These risk factors, such as depression and vascular disease, do not affect all individuals in the same way, likely due to inter-individual differences in genetics. However, the precise nature of how genetic risk profiles interact with modifiable risk factors to affect brain health is poorly understood. Here we combine multiple data resources, including genotyping and postmortem gene expression, to map the genetic landscape of brain structure and identify 367 loci associated with cortical thickness and 13 loci associated with white matter hyperintensities (P < 5×10−8), with several loci also showing a significant association with cognitive funct

  • Genetic architecture of the white matter connectome of the human brain - Science advances (2023) · Sha Z, Schijven D, Fisher SE, Francks C · PubMed 36800424

    ABSTRACT: White matter tracts form the structural basis of large-scale brain networks. We applied brain-wide tractography to diffusion images from 30,810 adults (U.K. Biobank) and found significant heritability for 90 node-level and 851 edge-level network connectivity measures. Multivariate genome-wide association analyses identified 325 genetic loci, of which 80% had not been previously associated with brain metrics. Enrichment analyses implicated neurodevelopmental processes including neurogenesis, neural differentiation, neural migration, neural projection guidance, and axon development, as well as prenatal brain expression especially in stem cells, astrocytes, microglia, and neurons. The multivariate association profiles implicated 31 loci in connectivity between core regions of the le

  • 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

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