# Large-scale genomics unveil polygenic architecture of human cortical surface area

## TL;DR

This study shows that genetic variation across the genome significantly influences the surface area of the human cortex, with different brain regions being affected by different types of genetic regions.

## Contribution

The study reveals that polygenic effects and evolutionary conservation of genomic regions are linked to cortical surface area variation.

## Key findings

- SNPs across the genome explain a large proportion of cortical surface area variation, especially in sensory and insular cortices.
- Genetic effects are enriched in or near genes and in evolutionarily conserved regions, particularly for medial and temporal cortices.
- Less conserved genomic regions contribute more to variation in occipital and prefrontal cortices.

## Abstract

Little is known about how genetic variation contributes to neuroanatomical variability, and whether particular genomic regions comprising genes or evolutionarily conserved elements are enriched for effects that influence brain morphology. Here, we examine brain imaging and single-nucleotide polymorphisms (SNPs) data from ∼2,700 individuals. We show that a substantial proportion of variation in cortical surface area is explained by additive effects of SNPs dispersed throughout the genome, with a larger heritable effect for visual and auditory sensory and insular cortices (h2∼0.45). Genome-wide SNPs collectively account for, on average, about half of twin heritability across cortical regions (N=466 twins). We find enriched genetic effects in or near genes. We also observe that SNPs in evolutionarily more conserved regions contributed significantly to the heritability of cortical surface area, particularly, for medial and temporal cortical regions. SNPs in less conserved regions contributed more to occipital and dorsolateral prefrontal cortices.

How genetic variation contributes to brain morphology is still poorly understood. Here Chen et al. combine brain imaging with single-nucleotide polymorphism data to discover that a substantial degree of cortical variation is derived from underlying genetic differences.