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Mendelian randomisation analyses find pulmonary factors mediate the effect of height on coronary artery disease

Marouli, E., Del Greco, M. F., Astley, C. M., Yang, J., Ahmad, S., Berndt, S., Caulfield, M. J., Evangelou, E., McKnight, B., Medina-Gomez, C., van Vliet-Ostaptchouk, J. V., Warren, H. R., Zhu, Z., Hirschhorn, J. N., Loos, R. J. F., Kutalik, Z. & Deloukas, P., 27-Mar-2019, In : Communications biology. 2, 9 p., 119.

Research output: Contribution to journalArticleAcademicpeer-review

  • Eirini Marouli
  • M. Fabiola Del Greco
  • Christina M. Astley
  • Jian Yang
  • Shafqat Ahmad
  • Sonja Berndt
  • Mark J. Caulfield
  • Evangelos Evangelou
  • Barbara McKnight
  • Carolina Medina-Gomez
  • Jana V. van Vliet-Ostaptchouk
  • Helen R. Warren
  • Zhihong Zhu
  • Joel N. Hirschhorn
  • Ruth J. F. Loos
  • Zoltan Kutalik
  • Panos Deloukas

There is evidence that lower height is associated with a higher risk of coronary artery disease (CAD) and increased risk of type 2 diabetes (T2D). It is not clear though whether these associations are causal, direct or mediated by other factors. Here we show that one standard deviation higher genetically determined height (similar to 6.5 cm) is causally associated with a 16% decrease in CAD risk (OR = 0.84, 95% CI 0.80-0.87). This causal association remains after performing sensitivity analyses relaxing pleiotropy assumptions. The causal effect of height on CAD risk is reduced by 1-3% after adjustment for potential mediators (lipids, blood pressure, glycaemic traits, body mass index, socio-economic status). In contrast, our data suggest that lung function (measured by forced expiratory volume [FEV1] and forced vital capacity [FVC]) is a mediator of the effect of height on CAD. We observe no direct causal effect of height on the risk of T2D.

Original languageEnglish
Article number119
Number of pages9
JournalCommunications biology
Volume2
Publication statusPublished - 27-Mar-2019

    Keywords

  • MULTIPLE GENETIC-VARIANTS, INSTRUMENTAL VARIABLES, HEART-DISEASE, ASSOCIATION, RISK, BIAS, ATHEROSCLEROSIS, PLEIOTROPY, MORTALITY, SELECTION

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