. Identification of common variants associated with human hippocampal and intracranial volumes. Nat Genet. 2012;44(5):552-61. PubMed.

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  1. Head circumference is used as a measure of brain size and development in early childhood and normal variation in head circumference has been associated with cognitive and behavioral development. Larger head circumference in infancy is associated with higher IQ scores in childhood. However, the underlying mechanisms are poorly understood. The aim of this study was to identify common genetic variants which affect infant head circumference. In an international collaborative effort, involving studies from Europe, Australia, and the U.S., we performed a genome-wide association study on head circumference in infancy. We reasoned that finding such variants might lead to new insights into important mechanisms for the development of the brain.

    We found two loci on chromosome 12 related to head circumference. These two regions previously were associated with adult height, suggesting the findings might reflect an overall effect of skeletal growth on head size. Interestingly, another paper in the same issue of Nature Genetics found the same region near the gene HMGA2 to be associated with intra-cranial volume, a measure of maximum brain size. We also found suggestive evidence that a region on chromosome 17, which includes many genes previously indicated to be involved in neurodegenerative diseases, might affect infant head circumference. This interesting region on chromosome 17 was also associated with intra-cranial volume in the accompanying paper by Ikram et al.

    These findings might suggest that genes in this region have an effect on brain growth in early life and neurological disease in later life. However, from these studies we cannot conclude that brain growth in early life is directly related to neurological disease risk in later life. These findings give clues for further research to investigate exact underlying consequences of these associations, investigate if specific parts of the brain or brain development are involved, and how this affects neurodevelopment in early and later life. The results of the studies and future studies might add new pieces to help unravel the puzzle of the etiology of neurodegenerative diseases.

    View all comments by Rob Taal

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  1. GWAS and Anatomy—Pooled Data Finger Genes Driving Brain Size, IQ