Evidence map›Paper›PMID 42697192›Full record

ArticleAmerican journal of human genetics2026

Beyond exons: Linking noncoding heritability and polygenicity across complex human traits and disorders.

Julian Fuhrer, Alexey A Shadrin, Timothy Hughes, Nadine Parker, Guy Hindley, Evgeniia Frei, Dat Nguyen, Olav B Smeland, Srdjan Djurovic, Ole A Andreassen and 2 more

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In one paragraph

Article in American journal of human genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Julian FuhrerCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: julian.fuhrer@medisin.uio.no.
Alexey A ShadrinCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo and Oslo University Hospital, Oslo, Norway.
Timothy HughesDepartment of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
Nadine ParkerCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Guy HindleyCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Evgeniia FreiCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Dat NguyenCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Olav B SmelandCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Srdjan DjurovicCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
Ole A AndreassenCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Anders M DaleCenter for Multimodal Imaging and Genetics, J. Craig Venter Institute, La Jolla, CA, USA; University of California, San Diego, La Jolla, CA, USA; University of Oslo, Oslo, Norway.
Oleksandr FreiCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Pharmacy, Section for Pharmacology and Pharmaceutical Biosciences, University of Oslo, Oslo, Norway. Electronic address: oleksandr.frei@medisin.uio.no.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The genetic architecture of complex traits spans a continuum of polygenicity, yet it remains unclear how differences in polygenicity relate to the functional localization of SNP heritability across the genome. We use a MiXeR-based framework to partition heritability across 74 functional annotations covering exonic, intronic, and intergenic regions for 34 complex traits and introduce a likelihood-based annotation contribution score that quantifies annotation-specific impact on heritability. Exons account for a minority of heritability, and their contribution decreases with increasing polygenicity, from an average of 22% in less-polygenic somatic diseases and biomarkers to 13% in highly polygenic psychiatric and cognitive phenotypes. Intergenic fractions show the opposite trend, whereas intronic fractions remain relatively stable. Analysis of the broader set of functional annotations also reveals systematic differences along the polygenicity axis: highly polygenic traits show stronger contributions from comparative genomics and variant-effect scores, whereas less-polygenic traits show stronger contributions from promoter, transcription, and chromatin annotations. Together, these results indicate that the functional partitioning of heritability systematically varies with polygenicity, shifting from gene-proximal regulatory architectures to architectures shaped by numerous dispersed regulatory effects.

Indexed as

ExonsMultifactorial InheritanceDNA, IntergenicGenome, HumanHumansIntronsMolecular Sequence AnnotationPhenotypePolymorphism, Single NucleotideDNA, Intergenicannotation contribution scoreevolutionary conservationfunctional annotationsgenetic architectureintergenic regionMiXeRnoncoding genomepolygenicitypsychiatric disordersSNP heritability

Identifiers

PMID42697192

What OpenQuestion holds

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Registered trials

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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.