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Nicotine binds to and activates the nicotinic acetylcholine receptors (present abundantly in the central and peripheral nervous systems) and thus increases intracellular calcium and leads to downstream activation of cAMP response element-binding protein, a key transcription factor for many genes (Shen and Yakel, 2009)

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Mendelian randomization case-control PheWAS in UK Biobank shows evidence of causality for smoking intensity in 28 distinct clinical conditions