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This surrogacy is especially robust for rare, monogenic variants with large effect sizes, which are more likely to exhibit Mendelian patterns of inheritance within families than common variants with individually small effect sizes

[26] on the other hand, only examined current e-cigarette use, without accounting for prior smoking history: had there been a significant association between e-cigarette use and onset of respiratory symptoms, it could be due to prior cigarette smoking, in which case adjusting for pack-years would be necessary (though not necessarily sufficient) to account for this [14]

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