Birthweight, BMI in adulthood and latent autoimmune diabetes in adults : a Mendelian randomisation study
Wei, Yuxia ; Zhan, Yiqiang ; Löfvenborg, Josefin E. ; Tuomi, Tiinamaija LU
and Carlsson, Sofia
(2022)
In Diabetologia
65(9).
p.1510-1518
- Abstract
Aims/hypothesis: Observational studies have found an increased risk of latent autoimmune diabetes in adults (LADA) associated with low birthweight and adult overweight/obese status. We aimed to investigate whether these associations are causal, using a two-sample Mendelian randomisation (MR) design. In addition, we compared results for LADA and type 2 diabetes. Methods: We identified 43 SNPs acting through the fetal genome as instrumental variables (IVs) for own birthweight from a genome-wide association study (GWAS) of the Early Growth Genetics Consortium (EGG) and the UK Biobank. We identified 820 SNPs as IVs for adult BMI from a GWAS of the UK Biobank and the Genetic Investigation of ANthropometric Traits consortium (GIANT). Summary... (More)
Aims/hypothesis: Observational studies have found an increased risk of latent autoimmune diabetes in adults (LADA) associated with low birthweight and adult overweight/obese status. We aimed to investigate whether these associations are causal, using a two-sample Mendelian randomisation (MR) design. In addition, we compared results for LADA and type 2 diabetes. Methods: We identified 43 SNPs acting through the fetal genome as instrumental variables (IVs) for own birthweight from a genome-wide association study (GWAS) of the Early Growth Genetics Consortium (EGG) and the UK Biobank. We identified 820 SNPs as IVs for adult BMI from a GWAS of the UK Biobank and the Genetic Investigation of ANthropometric Traits consortium (GIANT). Summary statistics for the associations between IVs and LADA were extracted from the only GWAS involving 2634 cases and 5947 population controls. We used the inverse-variance weighted (IVW) estimator as our primary analysis, supplemented by a series of sensitivity analyses. Results: Genetically determined own birthweight was inversely associated with LADA (OR per SD [~500 g] decrease in birthweight 1.68 [95% CI 1.01, 2.82]). In contrast, genetically predicted BMI in adulthood was positively associated with LADA (OR per SD [~4.8 kg/m2] increase in BMI 1.40 [95% CI 1.14, 1.71]). Robust results were obtained in a range of sensitivity analyses using other MR estimators or excluding some IVs. With respect to type 2 diabetes, the association with birthweight was not stronger than in LADA while the association with adult BMI was stronger than in LADA. Conclusions/ interpretation: This study provides genetic support for a causal link between low birthweight, adult overweight/obese status and LADA. Graphical abstract: [Figure not available: see fulltext.]
(Less)
- author
- Wei, Yuxia
; Zhan, Yiqiang
; Löfvenborg, Josefin E.
; Tuomi, Tiinamaija
LU
and Carlsson, Sofia
- organization
- publishing date
- 2022-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Epidemiology, Genetics, Human, Weight regulation and obesity
- in
- Diabetologia
- volume
- 65
- issue
- 9
- pages
- 9 pages
- publisher
- Springer
- external identifiers
-
- pmid:35606578
- scopus:85130457011
- ISSN
- 0012-186X
- DOI
- 10.1007/s00125-022-05725-2
- language
- English
- LU publication?
- yes
- id
- 7fb2e61c-05f7-4dad-aa58-1e22d5d301b2
- date added to LUP
- 2022-09-15 12:55:57
- date last changed
- 2024-04-14 14:48:07
@article{7fb2e61c-05f7-4dad-aa58-1e22d5d301b2,
abstract = {{<p>Aims/hypothesis: Observational studies have found an increased risk of latent autoimmune diabetes in adults (LADA) associated with low birthweight and adult overweight/obese status. We aimed to investigate whether these associations are causal, using a two-sample Mendelian randomisation (MR) design. In addition, we compared results for LADA and type 2 diabetes. Methods: We identified 43 SNPs acting through the fetal genome as instrumental variables (IVs) for own birthweight from a genome-wide association study (GWAS) of the Early Growth Genetics Consortium (EGG) and the UK Biobank. We identified 820 SNPs as IVs for adult BMI from a GWAS of the UK Biobank and the Genetic Investigation of ANthropometric Traits consortium (GIANT). Summary statistics for the associations between IVs and LADA were extracted from the only GWAS involving 2634 cases and 5947 population controls. We used the inverse-variance weighted (IVW) estimator as our primary analysis, supplemented by a series of sensitivity analyses. Results: Genetically determined own birthweight was inversely associated with LADA (OR per SD [~500 g] decrease in birthweight 1.68 [95% CI 1.01, 2.82]). In contrast, genetically predicted BMI in adulthood was positively associated with LADA (OR per SD [~4.8 kg/m<sup>2</sup>] increase in BMI 1.40 [95% CI 1.14, 1.71]). Robust results were obtained in a range of sensitivity analyses using other MR estimators or excluding some IVs. With respect to type 2 diabetes, the association with birthweight was not stronger than in LADA while the association with adult BMI was stronger than in LADA. Conclusions/ interpretation: This study provides genetic support for a causal link between low birthweight, adult overweight/obese status and LADA. Graphical abstract: [Figure not available: see fulltext.]</p>}},
author = {{Wei, Yuxia and Zhan, Yiqiang and Löfvenborg, Josefin E. and Tuomi, Tiinamaija and Carlsson, Sofia}},
issn = {{0012-186X}},
keywords = {{Epidemiology; Genetics; Human; Weight regulation and obesity}},
language = {{eng}},
number = {{9}},
pages = {{1510--1518}},
publisher = {{Springer}},
series = {{Diabetologia}},
title = {{Birthweight, BMI in adulthood and latent autoimmune diabetes in adults : a Mendelian randomisation study}},
url = {{http://dx.doi.org/10.1007/s00125-022-05725-2}},
doi = {{10.1007/s00125-022-05725-2}},
volume = {{65}},
year = {{2022}},
}