Age-dependent effects of body mass index across the adult life span on the risk of dementia: a cohort study with a genetic approach
Age-dependent effects of body mass index across the adult life span on the risk of dementia: a cohort study with a genetic approach
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DOI：
10.1186/s12916-020-01600-2
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发表时间：
2020-06-09
期刊：
影响因子：
9.3
通讯作者：
Dahl Aslan, Anna K.
中科院分区：
文献类型：
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作者：
Karlsson, Ida K.;Lehto, Kelli;Dahl Aslan, Anna K.
虽然中年时的高体重指数（BMI）与痴呆的高风险相关，但晚年的高BMI可能与较低的风险相关。本研究将遗传设计与纵向数据相结合，以更好地理解这一悖论。方法我们使用了来自瑞典双胞胎登记处（STR）的22，156名个体和来自健康与退休研究（HRS）的25，698名个体的纵向数据。STR样本有从成年早期到晚年的BMI信息，HRS样本从50岁到晚年。生存分析用于调查BMI和痴呆风险之间的年龄特异性关联。为了检查这些关联是否受到对较高BMI的遗传易感性的影响，BMI和BMI的多基因评分（PGS（BMI））之间的相互作用被纳入模型中，结果被分层为具有低、中、高BMI遗传易感性的人群。在STR中，应用共双胞胎控制模型来调整PGS（BMI）捕获的家族因素之外的家族因素。结果在35-49岁年龄段，BMI高5个单位与STR中痴呆风险增加15%（95%CI 7-24%）相关，BMI与PGS（BMI）之间存在显著的交互作用（p = 0.04），且仅在具有低BMI遗传倾向的人群中存在这种关联（HR 1.38，95%CI 1.08-1.78）。双胞胎对照分析表明遗传影响。在两个样本中，80岁以后，BMI增加5个单位与痴呆症风险降低10-11%相关。在STR中，晚年BMI和PGS（BMI）之间存在显著的相互作用（p = 0.01），但在HRS中没有，仅在PGS（BMI）高的人群中存在负相关（HR 0.70，95% CI 0.52-0.94）。没有明显的遗传影响，从双胞胎控制模型的晚年体重指数。结论不仅BMI和痴呆之间的关联因BMI测量时的年龄而异，而且遗传影响的影响也不同。在STR中，这种关联仅存在于BMI与其遗传易感性方向相反的人群中，这表明BMI与整个生命过程中的痴呆症之间的关联可能是由环境因素驱动的，因此可能是可以改变的。
Background While a high body mass index (BMI) in midlife is associated with higher risk of dementia, high BMI in late-life may be associated with lower risk. This study combined genetic designs with longitudinal data to achieve a better understanding of this paradox. Methods We used longitudinal data from 22,156 individuals in the Swedish Twin Registry (STR) and 25,698 from the Health and Retirement Study (HRS). The STR sample had information about BMI from early adulthood through late-life, and the HRS sample from age 50 through late-life. Survival analysis was applied to investigate age-specific associations between BMI and dementia risk. To examine if the associations are influenced by genetic susceptibility to higher BMI, an interaction between BMI and a polygenic score for BMI (PGS(BMI)) was included in the models and results stratified into those with genetic predisposition to low, medium, and higher BMI. In the STR, co-twin control models were applied to adjust for familial factors beyond those captured by the PGS(BMI). Results At age 35-49, 5 units higher BMI was associated with 15% (95% CI 7-24%) higher risk of dementia in the STR. There was a significant interaction (p = 0.04) between BMI and the PGS(BMI), and the association present only among those with genetic predisposition to low BMI (HR 1.38, 95% CI 1.08-1.78). Co-twin control analyses indicated genetic influences. After age 80, 5 units higher BMI was associated with 10-11% lower risk of dementia in both samples. There was a significant interaction between late-life BMI and the PGS(BMI) in the STR (p = 0.01), but not the HRS, with the inverse association present only among those with a high PGS(BMI) (HR 0.70, 95% CI 0.52-0.94)(.) No genetic influences were evident from co-twin control models of late-life BMI. Conclusions Not only does the association between BMI and dementia differ depending on age at BMI measurement, but also the effect of genetic influences. In STR, the associations were only present among those with a BMI in opposite direction of their genetic predisposition, indicating that the association between BMI and dementia across the life course might be driven by environmental factors and hence likely modifiable.