A role for HLA-DRB1*1101 and DRB1*0801 in cognitive ability and its decline with age.
A role for HLA-DRB1*1101 and DRB1*0801 in cognitive ability and its decline with age.
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HLA-DRB1*1101 和 DRB1*0801 在认知能力及其随年龄下降中的作用。
DOI：
10.1002/ajmg.b.32393
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Payton A
中科院分区：
文献类型：
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作者：
Payton A
认知能力（记忆力、处理速度、词汇量和流体智力）与教育程度和职业地位以及身心健康相关。在人群中观察到的认知能力的变化具有相当大的遗传贡献（遗传力<50%），然而，迄今为止，从全基因组关联和候选研究中识别的遗传多态性仅发现了有限数量的遗传变异，这些遗传变异产生的遗传效应很小。在这里，我们使用来自1，559名非病理性老年志愿者的现有全基因组关联数据来估算人类白细胞抗原（HLA），这些志愿者在12至18年间接受了认知功能变化的随访。具体来说，我们研究了DRB 1 *05（*11/*12）和DRB 1 *01，它们以前与认知能力有关。我们还分析了DRB 1 *0801，它与DRB 1 *1101具有密切的序列同源性。与DRB 1 *1101一起，DRB 1 *0801与几种疾病有关，包括多发性硬化和原发性胆汁性肝硬化，这些疾病本身与认知障碍有关。我们观察到DRB 1 *0801和DRB 1 *1101都与词汇能力（横截面和纵向得分）显著相关，并且DRB 1 *0801的影响方向相反，与得分较低和下降较快相关。这种相反的影响与系统性红斑狼疮、1型糖尿病和原发性胆汁性肝硬化的其他研究相似。DRB 1 *0801也与记忆能力下降显著相关。我们观察到认知能力与DRB 1 *01或DRB 1 *12之间没有关联。© 2015 Wiley Periodicals，Inc.
Cognitive abilities (memory, processing speed, vocabulary, and fluid intelligence) are correlated with educational attainment and occupational status, as well as physical and mental health. The variation in cognitive abilities observed within a population has a substantial genetic contribution (heritability ∼50%) and yet the identification of genetic polymorphisms from both genome‐wide association and candidate studies have to date only uncovered a limited number of genetic variants that exert small genetic effects. Here we impute human leukocyte antigens (HLA) using existing genome‐wide association data from 1,559 non‐pathological elderly volunteers who have been followed for changes in cognitive functioning between a 12‐ and 18‐year period. Specifically, we investigate DRB1*05 (*11/*12) and DRB1*01, which have previously been associated with cognitive ability. We also analyze DRB1*0801, which shares close sequence homology with DRB1*1101. Together with DRB1*1101, DRB1*0801 has been associated with several diseases including multiple sclerosis and primary biliary cirrhosis, which themselves are associated with cognitive impairment. We observed that both DRB1*0801 and DRB1*1101 were significantly associated with vocabulary ability (cross‐sectional and longitudinal scores) and that the effects were in opposite directions with DRB1*0801 associated with lower score and faster decline. This opposing affect is similar to that reported by other groups in systemic lupus erythematosus, type 1 diabetes, and primary biliary cirrhosis. DRB1*0801 was also significantly associated with reduced memory ability. We observed no associations between cognitive abilities and DRB1*01 or DRB1*12. © 2015 Wiley Periodicals, Inc.