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To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
Ocean Drilling Program Site 1085 provides a continuous marine sediment record off southern South West Africa for at least the last three and half million years. The n-alkane partial derivative(13) C record from this site records changes in past vegetation and provides an indication of the moisture availability of SW Africa during this time period. Very little variation, and no apparent trend, is observed in the n-alkane delta C-13 record, suggesting stable long-term conditions despite significant changes in East African tectonics and global climate. Slightly higher n-alkane delta C-13 values occur between 3.5 and 2.7 Ma suggesting slightly drier conditions than today. Between 2.5 and 2.7 Ma there is a shift to more negative n-alkane delta C-13 values suggesting slightly wetter conditions during a similar to 0.2 Ma episode that coincides with the intensification of Northern Hemisphere Glaciation (iNHG). From 2.5 to 0.4 Ma the n-alkane delta C-13 values are very consistent, varying by less than +/- 0.5 parts per thousand and suggesting little or no long-term change in the moisture availability of South West Africa over the last 2.5 million years. This is in contrast to the long-term drying trend observed further north offshore from the Namib Desert and in East Africa. A comparison of the climate history of these regions suggests that Southern Africa may have been an area of long-term stability over the last 3.5 Myrs.