Adult height and risk of 50 diseases: a combined epidemiological and genetic analysis

Florence Y Lai; Mintu Nath; Stephen E Hamby; John R Thompson; Christopher P Nelson; Nilesh J Samani

doi:10.1186/s12916-018-1175-7

Adult height and risk of 50 diseases: a combined epidemiological and genetic analysis

Florence Y Lai, Mintu Nath, Stephen E Hamby, John R Thompson, Christopher P Nelson, Nilesh J Samani^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

BACKGROUND: Adult height is associated with risk of several diseases, but the breadth of such associations and whether these associations are primary or due to confounding are unclear. We examined the association of adult height with 50 diseases spanning multiple body systems using both epidemiological and genetic approaches, the latter to identify un-confounded associations and possible underlying mechanisms.

METHODS: We examined the associations for adult height (using logistic regression adjusted for potential confounders) and genetically determined height (using a two-sample Mendelian randomisation approach with height-associated genetic variants as instrumental variables) in 417,434 individuals of white ethnic background participating in the UK Biobank. We undertook pathway analysis of height-associated genes to identify biological processes that could link height and specific diseases.

RESULTS: Height was associated with 32 diseases and genetically determined height associated with 12 diseases. Of these, 11 diseases showed a concordant association in both analyses, with taller height associated with reduced risks of coronary artery disease (odds ratio per standard deviation (SD) increase in height ORepi = 0.80, 95% CI 0.78-0.81; OR per SD increase in genetically determined height ORgen = 0.86, 95% CI 0.82-0.90), hypertension (ORepi = 0.83, 95% CI 0.82-0.84; ORgen = 0.88, 95% CI 0.85-0.91), gastro-oesophageal reflux disease (ORepi = 0.85, 95% CI 0.84-0.86; ORgen = 0.94, 95% CI 0.92-0.97), diaphragmatic hernia (ORepi = 0.81, 95% CI 0.79-0.82; ORgen = 0.91, 95% CI 0.88-0.94), but increased risks of atrial fibrillation (ORepi = 1.42, 95% CI 1.38-1.45; ORgen = 1.33, 95% CI 1.26-1.40), venous thromboembolism (ORepi = 1.18, 95% CI 1.16-1.21; ORgen = 1.15, 95% CI 1.11-1.19), intervertebral disc disorder (ORepi = 1.15, 95% CI 1.13-1.18; ORgen = 1.14, 95% CI 1.09-1.20), hip fracture (ORepi = 1.19, 95% CI 1.12-1.26; ORgen = 1.27, 95% CI 1.17-1.39), vasculitis (ORepi = 1.15, 95% CI 1.11-1.19; ORgen = 1.20, 95% CI 1.14-1.28), cancer overall (ORepi = 1.09, 95% CI 1.08-1.11; ORgen = 1.06, 95% CI 1.04-1.08) and breast cancer (ORepi = 1.08, 95% CI 1.06-1.10; ORgen = 1.07, 95% CI 1.03-1.11). Pathway analysis showed multiple height-associated pathways associating with individual diseases.

CONCLUSIONS: Adult height is associated with risk of a range of diseases. We confirmed previously reported height associations for coronary artery disease, atrial fibrillation, venous thromboembolism, intervertebral disc disorder, hip fracture and cancer and identified potential novel associations for gastro-oesophageal reflux disease, diaphragmatic hernia and vasculitis. Multiple biological mechanisms affecting height may affect the risks of these diseases.

Original language	English
Article number	187
Number of pages	18
Journal	BMC medicine
Volume	16
DOIs	https://doi.org/10.1186/s12916-018-1175-7
Publication status	Published - 25 Oct 2018

Bibliographical note

Funding
FYL and SEH are funded by the National Institute for Health Research Leicester Biomedical Research Centre. CPN and NJS are funded by the British Heart Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Availability of data and materials
The data reported in this paper are available via application directly to the UK Biobank.

Keywords

Adult
Aged
Body Height/genetics
Disease/etiology
Female
Genetic Testing/methods
Humans
Male
Mendelian Randomization Analysis/methods
Middle Aged
Risk Factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12916-018-1175-7Licence: CC BY

Adult height and risk of 50 diseases
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Final published version, 1.52 MBLicence: CC BY

Mintu Nath
- School of Medicine, Medical Sciences & Nutrition, Applied Health Sciences - Senior Lecturer
- School of Medicine, Medical Sciences & Nutrition, Medical Statistics
Person: Academic

Cite this

@article{78dd31ff9b084f11a5a4240008022285,

title = "Adult height and risk of 50 diseases: a combined epidemiological and genetic analysis",

abstract = "BACKGROUND: Adult height is associated with risk of several diseases, but the breadth of such associations and whether these associations are primary or due to confounding are unclear. We examined the association of adult height with 50 diseases spanning multiple body systems using both epidemiological and genetic approaches, the latter to identify un-confounded associations and possible underlying mechanisms.METHODS: We examined the associations for adult height (using logistic regression adjusted for potential confounders) and genetically determined height (using a two-sample Mendelian randomisation approach with height-associated genetic variants as instrumental variables) in 417,434 individuals of white ethnic background participating in the UK Biobank. We undertook pathway analysis of height-associated genes to identify biological processes that could link height and specific diseases.RESULTS: Height was associated with 32 diseases and genetically determined height associated with 12 diseases. Of these, 11 diseases showed a concordant association in both analyses, with taller height associated with reduced risks of coronary artery disease (odds ratio per standard deviation (SD) increase in height ORepi = 0.80, 95% CI 0.78-0.81; OR per SD increase in genetically determined height ORgen = 0.86, 95% CI 0.82-0.90), hypertension (ORepi = 0.83, 95% CI 0.82-0.84; ORgen = 0.88, 95% CI 0.85-0.91), gastro-oesophageal reflux disease (ORepi = 0.85, 95% CI 0.84-0.86; ORgen = 0.94, 95% CI 0.92-0.97), diaphragmatic hernia (ORepi = 0.81, 95% CI 0.79-0.82; ORgen = 0.91, 95% CI 0.88-0.94), but increased risks of atrial fibrillation (ORepi = 1.42, 95% CI 1.38-1.45; ORgen = 1.33, 95% CI 1.26-1.40), venous thromboembolism (ORepi = 1.18, 95% CI 1.16-1.21; ORgen = 1.15, 95% CI 1.11-1.19), intervertebral disc disorder (ORepi = 1.15, 95% CI 1.13-1.18; ORgen = 1.14, 95% CI 1.09-1.20), hip fracture (ORepi = 1.19, 95% CI 1.12-1.26; ORgen = 1.27, 95% CI 1.17-1.39), vasculitis (ORepi = 1.15, 95% CI 1.11-1.19; ORgen = 1.20, 95% CI 1.14-1.28), cancer overall (ORepi = 1.09, 95% CI 1.08-1.11; ORgen = 1.06, 95% CI 1.04-1.08) and breast cancer (ORepi = 1.08, 95% CI 1.06-1.10; ORgen = 1.07, 95% CI 1.03-1.11). Pathway analysis showed multiple height-associated pathways associating with individual diseases.CONCLUSIONS: Adult height is associated with risk of a range of diseases. We confirmed previously reported height associations for coronary artery disease, atrial fibrillation, venous thromboembolism, intervertebral disc disorder, hip fracture and cancer and identified potential novel associations for gastro-oesophageal reflux disease, diaphragmatic hernia and vasculitis. Multiple biological mechanisms affecting height may affect the risks of these diseases.",

keywords = "Adult, Aged, Body Height/genetics, Disease/etiology, Female, Genetic Testing/methods, Humans, Male, Mendelian Randomization Analysis/methods, Middle Aged, Risk Factors",

author = "Lai, {Florence Y} and Mintu Nath and Hamby, {Stephen E} and Thompson, {John R} and Nelson, {Christopher P} and Samani, {Nilesh J}",

note = "Funding FYL and SEH are funded by the National Institute for Health Research Leicester Biomedical Research Centre. CPN and NJS are funded by the British Heart Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Availability of data and materials The data reported in this paper are available via application directly to the UK Biobank.",

year = "2018",

month = oct,

day = "25",

doi = "10.1186/s12916-018-1175-7",

language = "English",

volume = "16",

journal = "BMC medicine ",

issn = "1741-7015",

publisher = "BioMed Central",

}

TY - JOUR

T1 - Adult height and risk of 50 diseases

T2 - a combined epidemiological and genetic analysis

AU - Lai, Florence Y

AU - Nath, Mintu

AU - Hamby, Stephen E

AU - Thompson, John R

AU - Nelson, Christopher P

AU - Samani, Nilesh J

N1 - Funding FYL and SEH are funded by the National Institute for Health Research Leicester Biomedical Research Centre. CPN and NJS are funded by the British Heart Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Availability of data and materials The data reported in this paper are available via application directly to the UK Biobank.

PY - 2018/10/25

Y1 - 2018/10/25

N2 - BACKGROUND: Adult height is associated with risk of several diseases, but the breadth of such associations and whether these associations are primary or due to confounding are unclear. We examined the association of adult height with 50 diseases spanning multiple body systems using both epidemiological and genetic approaches, the latter to identify un-confounded associations and possible underlying mechanisms.METHODS: We examined the associations for adult height (using logistic regression adjusted for potential confounders) and genetically determined height (using a two-sample Mendelian randomisation approach with height-associated genetic variants as instrumental variables) in 417,434 individuals of white ethnic background participating in the UK Biobank. We undertook pathway analysis of height-associated genes to identify biological processes that could link height and specific diseases.RESULTS: Height was associated with 32 diseases and genetically determined height associated with 12 diseases. Of these, 11 diseases showed a concordant association in both analyses, with taller height associated with reduced risks of coronary artery disease (odds ratio per standard deviation (SD) increase in height ORepi = 0.80, 95% CI 0.78-0.81; OR per SD increase in genetically determined height ORgen = 0.86, 95% CI 0.82-0.90), hypertension (ORepi = 0.83, 95% CI 0.82-0.84; ORgen = 0.88, 95% CI 0.85-0.91), gastro-oesophageal reflux disease (ORepi = 0.85, 95% CI 0.84-0.86; ORgen = 0.94, 95% CI 0.92-0.97), diaphragmatic hernia (ORepi = 0.81, 95% CI 0.79-0.82; ORgen = 0.91, 95% CI 0.88-0.94), but increased risks of atrial fibrillation (ORepi = 1.42, 95% CI 1.38-1.45; ORgen = 1.33, 95% CI 1.26-1.40), venous thromboembolism (ORepi = 1.18, 95% CI 1.16-1.21; ORgen = 1.15, 95% CI 1.11-1.19), intervertebral disc disorder (ORepi = 1.15, 95% CI 1.13-1.18; ORgen = 1.14, 95% CI 1.09-1.20), hip fracture (ORepi = 1.19, 95% CI 1.12-1.26; ORgen = 1.27, 95% CI 1.17-1.39), vasculitis (ORepi = 1.15, 95% CI 1.11-1.19; ORgen = 1.20, 95% CI 1.14-1.28), cancer overall (ORepi = 1.09, 95% CI 1.08-1.11; ORgen = 1.06, 95% CI 1.04-1.08) and breast cancer (ORepi = 1.08, 95% CI 1.06-1.10; ORgen = 1.07, 95% CI 1.03-1.11). Pathway analysis showed multiple height-associated pathways associating with individual diseases.CONCLUSIONS: Adult height is associated with risk of a range of diseases. We confirmed previously reported height associations for coronary artery disease, atrial fibrillation, venous thromboembolism, intervertebral disc disorder, hip fracture and cancer and identified potential novel associations for gastro-oesophageal reflux disease, diaphragmatic hernia and vasculitis. Multiple biological mechanisms affecting height may affect the risks of these diseases.

AB - BACKGROUND: Adult height is associated with risk of several diseases, but the breadth of such associations and whether these associations are primary or due to confounding are unclear. We examined the association of adult height with 50 diseases spanning multiple body systems using both epidemiological and genetic approaches, the latter to identify un-confounded associations and possible underlying mechanisms.METHODS: We examined the associations for adult height (using logistic regression adjusted for potential confounders) and genetically determined height (using a two-sample Mendelian randomisation approach with height-associated genetic variants as instrumental variables) in 417,434 individuals of white ethnic background participating in the UK Biobank. We undertook pathway analysis of height-associated genes to identify biological processes that could link height and specific diseases.RESULTS: Height was associated with 32 diseases and genetically determined height associated with 12 diseases. Of these, 11 diseases showed a concordant association in both analyses, with taller height associated with reduced risks of coronary artery disease (odds ratio per standard deviation (SD) increase in height ORepi = 0.80, 95% CI 0.78-0.81; OR per SD increase in genetically determined height ORgen = 0.86, 95% CI 0.82-0.90), hypertension (ORepi = 0.83, 95% CI 0.82-0.84; ORgen = 0.88, 95% CI 0.85-0.91), gastro-oesophageal reflux disease (ORepi = 0.85, 95% CI 0.84-0.86; ORgen = 0.94, 95% CI 0.92-0.97), diaphragmatic hernia (ORepi = 0.81, 95% CI 0.79-0.82; ORgen = 0.91, 95% CI 0.88-0.94), but increased risks of atrial fibrillation (ORepi = 1.42, 95% CI 1.38-1.45; ORgen = 1.33, 95% CI 1.26-1.40), venous thromboembolism (ORepi = 1.18, 95% CI 1.16-1.21; ORgen = 1.15, 95% CI 1.11-1.19), intervertebral disc disorder (ORepi = 1.15, 95% CI 1.13-1.18; ORgen = 1.14, 95% CI 1.09-1.20), hip fracture (ORepi = 1.19, 95% CI 1.12-1.26; ORgen = 1.27, 95% CI 1.17-1.39), vasculitis (ORepi = 1.15, 95% CI 1.11-1.19; ORgen = 1.20, 95% CI 1.14-1.28), cancer overall (ORepi = 1.09, 95% CI 1.08-1.11; ORgen = 1.06, 95% CI 1.04-1.08) and breast cancer (ORepi = 1.08, 95% CI 1.06-1.10; ORgen = 1.07, 95% CI 1.03-1.11). Pathway analysis showed multiple height-associated pathways associating with individual diseases.CONCLUSIONS: Adult height is associated with risk of a range of diseases. We confirmed previously reported height associations for coronary artery disease, atrial fibrillation, venous thromboembolism, intervertebral disc disorder, hip fracture and cancer and identified potential novel associations for gastro-oesophageal reflux disease, diaphragmatic hernia and vasculitis. Multiple biological mechanisms affecting height may affect the risks of these diseases.

KW - Adult

KW - Aged

KW - Body Height/genetics

KW - Disease/etiology

KW - Female

KW - Genetic Testing/methods

KW - Humans

KW - Male

KW - Mendelian Randomization Analysis/methods

KW - Middle Aged

KW - Risk Factors

U2 - 10.1186/s12916-018-1175-7

DO - 10.1186/s12916-018-1175-7

M3 - Article

C2 - 30355295

SN - 1741-7015

VL - 16

JO - BMC medicine

JF - BMC medicine

M1 - 187

ER -

Adult height and risk of 50 diseases: a combined epidemiological and genetic analysis

Abstract

Bibliographical note

Keywords

UN SDGs

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Mintu Nath

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