Summary: A new twin study reveals how genetics shape grey matter regions in the ageing human brain.
Source: University of New South Wales
UNSW Australia researchers have completed a landmark twin study examining genetic influences on key brain structures in people aged 65 and older.
An important international study of healthy older twins has provided new insight into how genes contribute to the development and variation of cortical and subcortical grey matter structures. These findings lay groundwork for mapping the genetic blueprint of the human brain.
A research team led by UNSW Medicine analysed MRI scans from 322 participants in the Older Australian Twins Study to estimate the heritability of twelve cortical and subcortical brain regions. These regions support functions ranging from memory and visual processing to motor control.
“We know genetics play a major role in brain development,” says lead researcher Associate Professor Wei Wen from the Centre for Healthy Brain Ageing (CHeBA) at UNSW. “But which genes contribute to specific brain structures, and whether the same genes influence multiple regions, has been unclear. This twin design lets us examine genetic correlations across the whole brain.”
The sample included 93 pairs of monozygotic (identical) twins and 68 pairs of dizygotic (fraternal) twins. Participants were Caucasian men and women without dementia, with an average age of 70, living in eastern Australia. The researchers measured volumes of twelve brain structures and used genetic and statistical modelling to estimate heritability — the proportion of observed variation attributable to genetic differences.
The study, published in Scientific Reports, reported several key findings:
- Cortical and subcortical volumes show moderate to strong genetic contributions, with heritability estimates generally between 40% and 80%;
- The hippocampus, a subcortical structure critical for memory, showed particularly high genetic influence—over 70% in older adults;
- Several cortical regions also demonstrated high heritability, including the frontal lobe (involved in movement, memory and motivation) and the occipital lobe (responsible for visual processing), both exceeding 70% genetic contribution;
- There is strong left-right symmetry: corresponding structures in the two hemispheres are influenced by the same genetic factors;
- Three genetically correlated clusters emerged across the brain, indicating groups of regions that appear to be affected by the same sets of genes. One cluster comprised the four cortical lobes, while the other two grouped distinct sets of subcortical structures.
“The discovery of three genetically correlated clusters is the most novel and important result,” says Scientia Professor Perminder Sachdev, neuropsychiatrist and co-director of CHeBA at UNSW. “It points to a new way of modelling the brain as subdivisions linked by shared genetic influences. That model can guide large-scale genetic studies aimed at identifying the specific genes that shape brain structure.”
Classical twin studies compare similarities between monozygotic twins, who share nearly all their DNA, and dizygotic twins, who share roughly half. When a trait is much more similar in identical twins than fraternal twins, it suggests a strong genetic basis. This study used that design to quantify genetic versus environmental contributions to regional brain volumes.
Despite the generally strong genetic influences, Sachdev notes a surprising finding: cortical and subcortical structures showed relatively low genetic correlation with each other. In other words, many cortical and subcortical regions appear to have largely distinct genetic determinants rather than a single shared genetic basis.
“This result reminds us that the brain is a highly complex organ and should not be treated as genetically uniform,” Sachdev adds. “Recognising region-specific genetic architecture is essential for understanding normal variation and the genetic pathways that may lead to neurological disease.”
Funding: The study involved collaborators at the University of Melbourne, the University of Queensland and the University of Montreal. The Older Australian Twins Study received support from the Australian Research Council and Australia’s National Health and Medical Research Council.
Source: Steve Offner – University of New South Wales
Original research: Full open-access article “Distinct Genetic Influences on Cortical and Subcortical Brain Structures” by Wei Wen and colleagues, published in Scientific Reports (2016).
University of New South Wales. “Twin Study Helps Unravel Genetic Blueprint of the Human Brain.” NeuroscienceNews. Published September 6, 2016.
Abstract
Distinct Genetic Influences on Cortical and Subcortical Brain Structures
This study assessed the heritability of grey matter regions in older adult twins (93 monozygotic and 68 dizygotic twin pairs; mean age 70 years) from the Older Australian Twins Study. Heritability estimates for subcortical regions ranged from 0.41 (amygdala) to 0.73 (hippocampus), while cortical regions ranged from 0.55 (parietal lobe) to 0.78 (frontal lobe). Corresponding structures in left and right hemispheres were influenced by the same genetic factors, showing high genetic correlations between hemispheric pairs. Three genetically correlated clusters were identified: (i) the cortical lobes (frontal, temporal, parietal and occipital); (ii) the basal ganglia (caudate, putamen and pallidum), which showed weak genetic links to cortical lobes; and (iii) a group comprising amygdala, hippocampus, thalamus and nucleus accumbens, which showed genetic correlations to both basal ganglia and cortical lobes, though relatively weak. The findings reveal a complex but patterned genetic architecture across the human brain, with distinct genetic determinants for cortical versus subcortical structures, notably the basal ganglia.
“Distinct Genetic Influences on Cortical and Subcortical Brain Structures” by Wei Wen et al., Scientific Reports (2016).