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Causal effect of adiposity measures on blood pressure traits in 2 urban swedish cohorts : A mendelian randomization study

Giontella, Alice LU orcid ; Lotta, Luca A. ; Overton, John D. ; Baras, Aris ; Minuz, Pietro ; Melander, Olle LU orcid ; Gill, Dipender and Fava, Cristiano LU (2021) In Journal of the American Heart Association 10(13).
Abstract

BACKGROUND: Different adiposity traits may be causally related to hypertension in different ways. By using genetic variants as randomly allocated proxies for studying the effect of modifying adiposity traits, the Mendelian randomization approach can be used to investigate this. METHODS AND RESULTS: In this study, we used 4 different genetic risk scores (GRS; GRS-BMI 565, GRS-WHR 324, GRS-VAT 208, GRS-BF 81) including hundreds of single nucleotide polymorphisms associated with body mass index, waist-to-hip ratio, visceral adipose tissue, and body fat, respectively. These were applied as instrumental variables in Mendelian randomization analyses. Two Swedish urban-based cohort studies, the Malmö Diet and Cancer, and the Malmö Preventive... (More)

BACKGROUND: Different adiposity traits may be causally related to hypertension in different ways. By using genetic variants as randomly allocated proxies for studying the effect of modifying adiposity traits, the Mendelian randomization approach can be used to investigate this. METHODS AND RESULTS: In this study, we used 4 different genetic risk scores (GRS; GRS-BMI 565, GRS-WHR 324, GRS-VAT 208, GRS-BF 81) including hundreds of single nucleotide polymorphisms associated with body mass index, waist-to-hip ratio, visceral adipose tissue, and body fat, respectively. These were applied as instrumental variables in Mendelian randomization analyses. Two Swedish urban-based cohort studies, the Malmö Diet and Cancer, and the Malmö Preventive Projects were used to obtain genetic association estimates with blood pressure (BP). In both the Malmö Preventive Projects and Malmö Diet and Cancer studies, except for that for body fat, all of the genetic risk scores were significantly associated with systolic BP and diastolic BP, but with different magnitudes. In particular, in both cohorts, each standard deviation increase in the genetic risk score made up by the 324 single nucleotide polymorphisms associated with waist-to-hip ratio was associated with doubling of the likelihood of hypertension prevalence at baseline. However, only the genetic risk score made up by the 565 SNPs associated with body mass index was significantly associated with hypertension incidence during 23.6±4.3 years of follow-up in the Malmö Preventive Project. CONCLUSIONS: We support a causal link between genetically mediated adiposity, especially waist-to-hip ratio and body mass index, and BP traits including hypertension prevalence and, for the first time to our knowledge, hypertension incidence. The differences in magnitude between these associations might suggest different mechanisms by which different adiposity affects BP/hypertension and consequently may indicate that tailored interventions are needed to reduce cardiovascular risk.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adiposity, Blood pressure, Genetics, Mendelian randomization, Polymorphisms
in
Journal of the American Heart Association
volume
10
issue
13
article number
e020405
publisher
Wiley-Blackwell
external identifiers
  • pmid:34120448
  • scopus:85110261108
ISSN
2047-9980
DOI
10.1161/JAHA.120.020405
project
MOVING FROM BIOMARKERS TO MECHANISM ORIENTED PREVENTION OF CARDIOMETABOLIC DISEASE
language
English
LU publication?
yes
id
3508ea8c-843f-4447-b09f-cb203f05dcad
date added to LUP
2021-09-07 22:53:06
date last changed
2024-04-06 08:21:12
@article{3508ea8c-843f-4447-b09f-cb203f05dcad,
  abstract     = {{<p>BACKGROUND: Different adiposity traits may be causally related to hypertension in different ways. By using genetic variants as randomly allocated proxies for studying the effect of modifying adiposity traits, the Mendelian randomization approach can be used to investigate this. METHODS AND RESULTS: In this study, we used 4 different genetic risk scores (GRS; GRS-BMI 565, GRS-WHR 324, GRS-VAT 208, GRS-BF 81) including hundreds of single nucleotide polymorphisms associated with body mass index, waist-to-hip ratio, visceral adipose tissue, and body fat, respectively. These were applied as instrumental variables in Mendelian randomization analyses. Two Swedish urban-based cohort studies, the Malmö Diet and Cancer, and the Malmö Preventive Projects were used to obtain genetic association estimates with blood pressure (BP). In both the Malmö Preventive Projects and Malmö Diet and Cancer studies, except for that for body fat, all of the genetic risk scores were significantly associated with systolic BP and diastolic BP, but with different magnitudes. In particular, in both cohorts, each standard deviation increase in the genetic risk score made up by the 324 single nucleotide polymorphisms associated with waist-to-hip ratio was associated with doubling of the likelihood of hypertension prevalence at baseline. However, only the genetic risk score made up by the 565 SNPs associated with body mass index was significantly associated with hypertension incidence during 23.6±4.3 years of follow-up in the Malmö Preventive Project. CONCLUSIONS: We support a causal link between genetically mediated adiposity, especially waist-to-hip ratio and body mass index, and BP traits including hypertension prevalence and, for the first time to our knowledge, hypertension incidence. The differences in magnitude between these associations might suggest different mechanisms by which different adiposity affects BP/hypertension and consequently may indicate that tailored interventions are needed to reduce cardiovascular risk.</p>}},
  author       = {{Giontella, Alice and Lotta, Luca A. and Overton, John D. and Baras, Aris and Minuz, Pietro and Melander, Olle and Gill, Dipender and Fava, Cristiano}},
  issn         = {{2047-9980}},
  keywords     = {{Adiposity; Blood pressure; Genetics; Mendelian randomization; Polymorphisms}},
  language     = {{eng}},
  number       = {{13}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of the American Heart Association}},
  title        = {{Causal effect of adiposity measures on blood pressure traits in 2 urban swedish cohorts : A mendelian randomization study}},
  url          = {{http://dx.doi.org/10.1161/JAHA.120.020405}},
  doi          = {{10.1161/JAHA.120.020405}},
  volume       = {{10}},
  year         = {{2021}},
}