A Twin Study of Sex Differences in Genetic Risk for All Dementia, Alzheimer's Disease (AD), and Non-AD Dementia.
A Twin Study of Sex Differences in Genetic Risk for All Dementia, Alzheimer's Disease (AD), and Non-AD Dementia.
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DOI：
10.3233/jad-191192
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Gatz M
中科院分区：
文献类型：
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作者：
Beam CR;Kaneshiro C;Jang JY;Reynolds CA;Pedersen NL;Gatz M
虽然阿尔茨海默病发病率的性别差异和可能的解释已经得到了相当大的关注，但对阿尔茨海默病遗传风险的性别差异可能引起的关注较少。我们检验了性别差异对所有痴呆、仅AD和非AD痴呆的疾病风险和发病年龄的遗传和环境影响。双胞胎是从瑞典双胞胎登记处挑选出来的。所有的痴呆症分析包括9,467对；仅AD，8,696对；以及非AD痴呆，8,195对。APOE分析包括1,923对带有测量到的ε4等位基因的双胞胎个体。痴呆症的诊断是基于临床检查和国家健康登记的联系。尽管所有痴呆症和仅有AD的女性的配对内相关性高于男性，但在所有痴呆症、仅AD和非AD痴呆症的遗传或环境病因方面，性别差异没有统计学差异。在观察特定遗传效应时，也观察到了类似的结果(APOEε4)。同卵双胞胎对照分析表明，在不符合痴呆症的双胞胎中，在第一个双胞胎确诊后的2-5年内，没有痴呆症的女性双胞胎患痴呆症的风险比男性高约40%。对于所有的痴呆症，只有阿尔茨海默病和非阿尔茨海默病，遗传影响可以在性别上等同。然而，同卵双胞胎的分析表明，女性比男性同卵双胞胎患痴呆症的风险更大，尽管遗传或共同环境对痴呆症风险的性别差异无法区分。
While sex differences in incidence of Alzheimer’s disease (AD) and potential explanations have received considerable attention, less attention has been paid to possible sex differences in genetic risk for AD. We examined sex differences in genetic and environmental influences on disease risk and age at onset for All Dementia, AD Only, and Non-AD Dementia. Twin pairs were drawn from the Swedish Twin Registry. All Dementia analysis included 9,467 pairs; AD only, 8,696 pairs; and non-AD dementia, 8,195 pairs. APOE analyses included 1,923 individual twins with measured ε4 alleles. Dementia diagnoses were based on clinical workup and national health registry linkage. Although within-pair correlations for All Dementia and AD Only were higher for women than for men, sex differences did not statistically differ for genetic or environmental etiology of All Dementia, AD Only, and Non-AD dementia. Similar results were observed when looking at specific genetic effects (APOE ε4). Co-twin control analyses indicated that among twin pairs discordant for dementia, female twins without dementia had approximately 40% greater risk of developing dementia, compared with their male counterparts, in the 2–5 years following the first twin’s diagnosis. For All Dementia, AD Only and Non-AD Dementia, genetic influences could be equated across sex. Co-twin analyses, however, suggest greater risk to female than to male co-twins of dementia cases even though sex differences in either genetic or shared environmental influences on the risk of dementia could not be differentiated.