Jakub Kopal

Using rare genetic mutations to revisit structural brain asymmetry

Jakub Kopal

Kuldeep Kumar

Kimia Shafighi

Karin Saltoun

Claudia Modenato

Clara A. Moreau

Guillaume Huguet

Martineau Jean-Louis

Charles-Olivier Martin

Zohra Saci

Nadine Younis

Élise Douard

Khadije Jizi

Alexis Beauchamp-Chatel

Leila Kushan

Ana I. Silva

Marianne B. M. van den Bree

David E. J. Linden

Michael J. Owen

Jeremy Hall … (see 10 more)

Sarah Lippé

Bogdan Draganski

Ida E. Sønderby

Ole A. Andreassen

David C. Glahn

Paul M. Thompson

Carrie E. Bearden

Robert Zatorre

Sébastien Jacquemont

Danilo Bzdok

Asymmetry between the left and right brain is a key feature of brain organization. Hemispheric functional specialization underlies some of t… (see more)he most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variant studies, which typically exert small effects on brain phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We quantitatively dissected the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior mapping highlights the consequences of genetically controlled brain lateralization on human-defining cognitive traits.

2023-04-17

bioRxiv (preprint)

doi.org

The end game: respecting major sources of population diversity

Jakub Kopal

Lucina Q. Uddin

Danilo Bzdok

Human neuroscience is enjoying burgeoning population data resources: large-scale cohorts with thousands of participant profiles of gene expr… (see more)ession, brain scanning and sociodemographic measures. The depth of phenotyping puts us in a better position than ever to fully embrace major sources of population diversity as effects of interest to illuminate mechanisms underlying brain health.

2023-03-02

Nature Methods (published)

doi.org

Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence

Jakub Kopal

Kuldeep Kumar

Karin Saltoun

Claudia Modenato

Clara Moreau

Sandra Martin‐Brevet

Guillaume Huguet

Martineau Jean‐Louis

Charles-Olivier Martin

Zohra Saci

Nadine Younis

Petra Tamer

Élise Douard

Anne Maillard

Borja Rodríguez‐Herreros

Aurélie Pain

Sonia Richetin

Leila Kushan

Ana Isabel Silva

Marianne van den Bree … (see 12 more)

David E.J. Linden

Michael J. Owen

Jeremy Hall

Sarah Lippé

Bogdan Draganski

Ida E. Sønderby

Ole A. Andreassen

David C. Glahn

Paul M. Thompson

Carrie E. Bearden

Sébastien Jacquemont

Danilo Bzdok

Copy number variations (CNVs) are rare genomic deletions and duplications that can affect brain and behaviour. Previous reports of CNV pleio… (see more)tropy imply that they converge on shared mechanisms at some level of pathway cascades, from genes to large-scale neural circuits to the phenome. However, existing studies have primarily examined single CNV loci in small clinical cohorts. It remains unknown, for example, how distinct CNVs escalate vulnerability for the same developmental and psychiatric disorders. Here we quantitatively dissect the associations between brain organization and behavioural differentiation across 8 key CNVs. In 534 CNV carriers, we explored CNV-specific brain morphology patterns. CNVs were characteristic of disparate morphological changes involving multiple large-scale networks. We extensively annotated these CNV-associated patterns with ~1,000 lifestyle indicators through the UK Biobank resource. The resulting phenotypic profiles largely overlap and have body-wide implications, including the cardiovascular, endocrine, skeletal and nervous systems. Our population-level investigation established brain structural divergences and phenotypical convergences of CNVs, with direct relevance to major brain disorders.

2023-03-01

Nature Human Behaviour (unknown)

doi.org

Endorsing Complexity Through Diversity: Computational Psychiatry Meets Big Data Analytics

Jakub Kopal

Danilo Bzdok

2022-08-04

Biological Psychiatry (unknown)

doi.org