Cortical differences across psychiatric disorders and associated common and rare genetic variants.

DOI
Publisher DOI
PubMed ID
40321288
Abstract
Genetic studies have identified common and rare variants increasing the risk for neurodevelopmental and psychiatric disorders (NPDs). These risk variants have also been shown to influence the structure of the cerebral cortex. However, it is unknown whether cortical differences associated with genetic variants are linked to the risk they confer for NPDs. To answer this question, we analyzed cortical thickness (CT) and surface area (SA) for common and rare variants associated with NPDs, in ~33000 individuals from the general population and clinical cohorts, as well as ENIGMA summary statistics for 8 NPDs. Rare and common genetic variants increasing risk for NPDs were preferentially associated with total SA, while NPDs were preferentially associated with mean CT. Larger effects on mean CT, but not total SA, were observed in NPD medicated subgroups. At the regional level, genetic variants were preferentially associated with effects in sensorimotor areas, while NPDs showed higher effects in association areas. We show that schizophrenia- and bipolar-disorder-associated SNPs show positive and negative effect sizes on SA suggesting that their aggregated effects cancel out in additive polygenic models. Overall, CT and SA differences associated with NPDs do not relate to those observed across individual genetic variants and may be linked with critical non-genetic factors, such as medication and the lived experience of the disorder.
Date Issued
2025-04-19
Publication Type
Working Paper
Language(s)
en
Author(s)
Kumar, Kuldeep
Liao, Zhijie
Kopal, Jakub
Moreau, Clara
Ching, Christopher R K
Modenato, Claudia
Snyder, Will
Kazem, Sayeh
Martin, Charles-Olivier
Bélanger, Anne-Marie
Fontaine, Valérie K
Jizi, Khadije
Boen, Rune
Huguet, Guillaume
Saci, Zohra
Kushan, Leila
Silva, Ana I
van den Bree, Marianne B M
Linden, David E J
Owen, Michael J
Hall, Jeremy
Lippé, Sarah
Dumas, Guillaume
Almasy, Laura
Thomopoulos, Sophia I
Jahanshad, Neda
Sønderby, Ida E
Andreassen, Ole A
Glahn, David C
Raznahan, Armin
Bearden, Carrie E
Paus, Tomas
Thompson, Paul M
Jacquemont, Sébastien
Additional Credits
Access(Rights)
open.access
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