Department of Epidemiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands.
Nat Genet. 2012 Apr 15;44(5):539-44. doi: 10.1038/ng.2245.
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 × 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 × 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 × 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 × 10(-3) for 6q22 and 1.2 × 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.
随着年龄的增长，颅内体积保持不变，代表着大脑所能达到的最大尺寸，而各种相互作用的生物现象导致脑容量的损失。因此，颅内体积和晚年的脑体积反映了不同的遗传影响。我们在 8175 名居住在社区的老年人中进行的全基因组关联研究（GWAS）没有发现任何与脑体积相关的全基因组显著关联（P<5×10(-8))。相比之下，颅内体积与两个位点显著相关：rs4273712（P=3.4×10(-11))，这是一个位于 6q22 染色体上的已知与身高相关的位点，以及 rs9915547（P=1.5×10(-12))，定位于 17q21 染色体的倒位上。我们在另一组 1752 名老年人中复制了这些与颅内体积相关的关联（6q22 的 P=1.1×10(-3)，17q21 的 P=1.2×10(-3)）。此外，我们还发现 17q21 位点与 10768 名儿童（平均年龄为 14.5 个月）的头围存在提示性关联。我们的数据确定了与头部大小相关的两个位点，17q21 上的倒位也可能参与了大脑最大尺寸的获得。
