Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato 09042, Italy.
Cell. 2013 Sep 26;155(1):242-56. doi: 10.1016/j.cell.2013.08.041.
The complex network of specialized cells and molecules in the immune system has evolved to defend against pathogens, but inadvertent immune system attacks on "self" result in autoimmune disease. Both genetic regulation of immune cell levels and their relationships with autoimmunity are largely undetermined. Here, we report genetic contributions to quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages. We first estimated trait heritability, showing that it can be substantial, accounting for up to 87% of the variance (mean 41%). Next, by assessing ∼8.2 million variants that we identified and confirmed in an extended set of 2,870 individuals, 23 independent variants at 13 loci associated with at least one trait. Notably, variants at three loci (HLA, IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease associations. These results connect specific cellular phenotypes to specific genetic variants, helping to explicate their involvement in disease.
免疫系统中专门的细胞和分子的复杂网络已经进化到可以抵御病原体，但免疫系统对“自身”的误攻击会导致自身免疫性疾病。免疫细胞水平的遗传调控及其与自身免疫的关系在很大程度上还没有确定。在这里，我们报告了在来自四个聚集的撒丁岛村庄的 1629 个人中，对 95 种细胞类型的 272 种免疫特征的定量水平的遗传贡献。我们首先估计了性状的遗传力，表明它可以很大，占方差的 41%（平均值）高达 87%。接下来，通过评估我们在一个扩展的 2870 人的集合中确定和确认的大约 820 万个变体，13 个位点的 23 个独立变体与至少一个特征相关。值得注意的是，三个位点（HLA、IL2RA 和 SH2B3/ATXN2）的变体与已知的自身免疫性疾病相关。这些结果将特定的细胞表型与特定的遗传变体联系起来，有助于阐明它们在疾病中的作用。
