Trial reportProceedings of the National Academy of Sciences of the United States of America2013
Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
88 citing papers in PubMed, 3 syntheses or guidelines pooled it, 164 citations in OpenAlex.
- CT1812 biomarker signature from a meta-analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- Gene co-expression changes underlying the functional connectomic alterations in Alzheimer's disease.BMC medical genomics · 2022Pooled it
- ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.Translational psychiatry · 2020Pooled it
- Protein co-aggregates of dense core amyloid plaques and CSF differ in rapidly progressive Alzheimer's disease and slower sporadic Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Exploratory analysis of the proteomic profile in plasma in adults with Down syndrome in the context of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Connecting intermediate phenotypes to disease using multi-omics in heart failure.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2025Article
- Accelerating Heritability, Genetic Correlation, and Genome-Wide Association Imaging Genetic Analyses in Complex Pedigrees.Human brain mapping · 2024Article
- Bayesian mixed model inference for genetic association under related samples with brain network phenotype.Biostatistics (Oxford, England) · 2024Article
- Biological Age, Chronological Age, and Survival in Pulmonary Fibrosis: A Causal Mediation Analysis.American journal of respiratory and critical care medicine · 2024Article
- Genetic architecture of the structural connectome.Nature communications · 2024Article
- Deriving comprehensive literature trends on multi-omics analysis studies in autism spectrum disorder using literature mining pipeline.Frontiers in neuroscience · 2024Article
- Current and future directions in network biology.Bioinformatics advances · 2024Article
- A review of brain imaging biomarker genomics in Alzheimer's disease: implementation and perspectives.Translational neurodegeneration · 2022Review
- Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain.Nature communications · 2022Article
- The human connectome in Alzheimer disease - relationship to biomarkers and genetics.Nature reviews. Neurology · 2021Review
- Peripheral Expression ofPsychiatry and clinical psychopharmacology · 2021Article
- Inter-individual body mass variations relate to fractionated functional brain hierarchies.Communications biology · 2021Article
- Heritability of Functional Connectivity in Resting State: Assessment of the Dynamic Mean, Dynamic Variance, and Static Connectivity across Networks.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Super-variants identification for brain connectivity.Human brain mapping · 2021Article
- Long runs of homozygosity are associated with Alzheimer's disease.Translational psychiatry · 2021Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 11 institutions in 2 countries.
Funding
Abstract
Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain's connectivity pattern, allowing us to discover genetic variants that affect the human brain's wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer's disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.