Exploring the association of genetic factors with participation in the Avon Longitudinal Study of Parents and Children.
Exploring the association of genetic factors with participation in the Avon Longitudinal Study of Parents and Children.
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DOI：
10.1093/ije/dyy060
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发表时间：
2018-08-01
影响因子：
7.7
通讯作者：
Tilling K
中科院分区：
文献类型：
--
作者：
Taylor AE;Jones HJ;Sallis H;Euesden J;Stergiakouli E;Davies NM;Zammit S;Lawlor DA;Munafò MR;Davey Smith G;Tilling K
人们通常认为，选择(包括参与和退出)并不代表基因研究中偏见的一个重要来源。然而，迄今为止，关于遗传因素对参与的影响的证据很少。使用雅芳亲子纵向研究的母亲(N = 7486)和孩子(N = 7508)的数据，我们：(I)研究了一系列社会人口和生活方式特征的多基因风险分数与持续参与相关的健康状况的关联；(Ii)调查了多基因分数与体重指数(BMI；来自自我报告的体重和身高)和自我报告吸烟的关系是否在最大样本中与遗传数据和参与最近一次随访的子样本中有所不同；以及(Iii)利用全基因组数据，确定了由常见遗传变异解释的参与变异的比例。我们发现有证据表明，高等教育、宜人性和开放性的多基因得分与较高的参与度相关；而开始吸烟、较高的BMI、神经质、精神分裂症、注意力缺陷多动障碍(ADHD)和抑郁症的多基因得分与较低的参与度相关。多基因教育得分与自我报告吸烟之间的关联在有遗传数据的最大样本[多基因得分中曾经吸烟的优势比(OR)：0.85，95%可信区间(CI)：0.81，0.89]和亚样本(OR：0.96，95%CI：0.89，1.03)之间存在差异。在全基因组分析中，基于单核苷酸多态的遗传性解释了参与的18-32%的变异性。遗传关联研究，包括孟德尔随机化，可能会因选择而产生偏差，包括对随访的损失。在选择性参与的所有研究分析中都应考虑辍学的遗传风险。
It is often assumed that selection (including participation and dropout) does not represent an important source of bias in genetic studies. However, there is little evidence to date on the effect of genetic factors on participation. Using data on mothers (N = 7486) and children (N = 7508) from the Avon Longitudinal Study of Parents and Children, we: (i) examined the association of polygenic risk scores for a range of sociodemographic and lifestyle characteristics and health conditions related to continued participation; (ii) investigated whether associations of polygenic scores with body mass index (BMI; derived from self-reported weight and height) and self-reported smoking differed in the largest sample with genetic data and a subsample who participated in a recent follow-up; and (iii) determined the proportion of variation in participation explained by common genetic variants, using genome-wide data. We found evidence that polygenic scores for higher education, agreeableness and openness were associated with higher participation; and polygenic scores for smoking initiation, higher BMI, neuroticism, schizophrenia, attention-deficit hyperactivity disorder (ADHD) and depression were associated with lower participation. Associations between the polygenic score for education and self-reported smoking differed between the largest sample with genetic data [odds ratio (OR) for ever smoking per standard deviation (SD) increase in polygenic score: 0.85, 95% confidence interval (CI): 0.81, 0.89} and subsample (OR: 0.96, 95% CI: 0.89, 1.03). In genome-wide analysis, single nucleotide polymorphism based heritability explained 18–32% of variability in participation. Genetic association studies, including Mendelian randomization, can be biased by selection, including loss to follow-up. Genetic risk for dropout should be considered in all analyses of studies with selective participation.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
DOI：
10.1093/bioinformatics/btu848
发表时间：
2015-05-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Euesden J;Lewis CM;O'Reilly PF
通讯作者：
O'Reilly PF
DOI：
10.1097/ede.0b013e3181d61eeb
发表时间：
2010-05
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Lipsitch M;Tchetgen Tchetgen E;Cohen T
通讯作者：
Cohen T
影响因子：
11
作者：
通讯作者：
--
影响因子：
9.8
作者：
Palla, Luigi;Dudbridge, Frank
通讯作者：
Dudbridge, Frank