Birth weight is positively associated with adult osteoporosis risk: observational and Mendelian randomization studies

2021 ◽  
Author(s):  
Xing‐Hao Yu ◽  
Yong‐Yue Wei ◽  
Ping Zeng ◽  
Shu‐Feng Lei
Keyword(s):  
Birth Weight ◽  
Mendelian Randomization ◽  
Osteoporosis Risk

scholarly journals Using a two-sample Mendelian randomization design to investigate a possible causal effect of maternal lipid concentrations on offspring birth weight

2019 ◽  
Vol 48 (5) ◽  
pp. 1457-1467 ◽  
Author(s):  
Liang-Dar Hwang ◽  
Deborah A Lawlor ◽  
Rachel M Freathy ◽  
David M Evans ◽  
Nicole M Warrington
Keyword(s):  
Birth Weight ◽  
Standard Deviation ◽  
Structural Equation ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
European Ancestry ◽  
The Impact

Abstract Background The intrauterine environment is critical for fetal growth and development. However, observational associations between maternal gestational lipid concentrations and offspring birth weight (BW) have been inconsistent and ascertaining causality is challenging. Methods We used a novel two-sample Mendelian randomization (MR) approach to estimate the causal effect of maternal gestational high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride concentrations on offspring BW. Single nucleotide polymorphisms (SNPs) associated with serum HDL-C, LDL-C and triglyceride concentrations identified in the Global Lipids Genetics Consortium genome-wide association study meta-analysis (n = 188 577 European-ancestry individuals; sample 1) were selected as instrumental variables. The effects of these SNPs on offspring BW were estimated using a structural equation model in the UK Biobank and Early Growth Genetics consortium (n = 230 069 European-ancestry individuals; sample 2) that enabled partitioning of the genetic associations into maternal- (intrauterine) and fetal-specific effects. Results We found no evidence for a causal effect of maternal gestational HDL-C, LDL-C or triglyceride concentrations on offspring BW [standard deviation change in BW per standard deviation higher in HDL-C = −0.005 (95% confidence interval: −0.039, 0.029), LDL-C = 0.014 (−0.017, 0.045), and triglycerides = 0.014 (−0.025, 0.052)]. Conclusions Our findings suggest that maternal gestational HDL-C, LDL-C and triglyceride concentrations play a limited role in determining offspring BW. However, we cannot comment on the impact of these and other lipid fractions on fetal development more generally. Our study illustrates the power and flexibility of two-sample MR in assessing the causal effect of maternal environmental exposures on offspring outcomes.

scholarly journals Relationship between birth weight and chronic kidney disease: evidence from systematics review and two-sample Mendelian randomization analysis

2020 ◽  
Vol 29 (13) ◽  
pp. 2261-2274 ◽  
Author(s):  
Xinghao Yu ◽  
Zhongshang Yuan ◽  
Haojie Lu ◽  
Yixin Gao ◽  
Haimiao Chen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Birth Weight ◽  
Kidney Disease ◽  
Low Birth Weight ◽  
Kidney Function ◽  
Large Scale ◽  
Mendelian Randomization ◽  
Negative Relationship ◽  
Sensitivity Analyses ◽  
Inverse Association

Abstract Observational studies showed an inverse association between birth weight and chronic kidney disease (CKD) in adulthood existed. However, whether such an association is causal remains fully elusive. Moreover, none of prior studies distinguished the direct fetal effect from the indirect maternal effect. Herein, we aimed to investigate the causal relationship between birth weight and CKD and to understand the relative fetal and maternal contributions. Meta-analysis (n = ~22 million) showed that low birth weight led to ~83% (95% confidence interval [CI] 37–146%) higher risk of CKD in late life. With summary statistics from large scale GWASs (n = ~300 000 for birth weight and ~481 000 for CKD), linkage disequilibrium score regression demonstrated birth weight had a negative maternal, but not fetal, genetic correlation with CKD and several other kidney-function related phenotypes. Furthermore, with multiple instruments of birth weight, Mendelian randomization showed there existed a negative fetal casual association (OR = 1.10, 95% CI 1.01–1.16) between birth weight and CKD; a negative but non-significant maternal casual association (OR = 1.09, 95% CI 0.98–1.21) was also identified. Those associations were robust against various sensitivity analyses. However, no maternal/fetal casual effects of birth weight were significant for other kidney-function related phenotypes. Overall, our study confirmed the inverse association between birth weight and CKD observed in prior studies, and further revealed the shared maternal genetic foundation between low birth weight and CKD, and the direct fetal and indirect maternal causal effects of birth weight may commonly drive this negative relationship.

Maternal polycystic ovary syndrome and offspring birth weight: a Mendelian randomization study

2021 ◽  
Author(s):  
Yuexin Gan ◽  
Donghao Lu ◽  
Chonghuai Yan ◽  
Jun Zhang ◽  
Jian Zhao
Keyword(s):  
Birth Weight ◽  
Polycystic Ovary Syndrome ◽  
Causal Relationship ◽  
Mendelian Randomization ◽  
Polycystic Ovary ◽  
Causal Effect ◽  
Sensitivity Analyses ◽  
European Ancestry ◽  
Ovary Syndrome ◽  
Genetic Instruments

Abstract Background Observational associations between maternal polycystic ovary syndrome (PCOS) and offspring birth weight (BW) have been inconsistent and the causal relationship is still uncertain. Objective We conducted a two-sample Mendelian randomization (MR) study to estimate the causal effect of maternal PCOS on offspring BW. Methods We constructed genetic instruments for PCOS with 14 single nucleotide polymorphisms (SNPs) which were identified in the genome-wide association study (GWAS) meta-analysis including 10,074 PCOS cases and 103,164 controls of European ancestry from seven cohorts. The genetic associations of these SNPs with the offspring BW were extracted from summary statistics estimated by the Early Growth Genetics (EGG) consortium (n = 406,063 European-ancestry individuals) using the weighted linear model (WLM), an approximation method of structural equation model (SEM), which separated maternal genetic effects from fetal genetic effects. We used a two-sample MR design to examine the causal relationship between maternal PCOS and offspring BW. Sensitivity analyses were conducted to assess the robustness of the MR results. Results We found little evidence for a causal effect of maternal PCOS on offspring BW (-6.1 g, 95% confidence interval [CI]: -16.8 g, 4.6 g). Broadly consistent results were found in the sensitivity analyses. Conclusion Despite the large scale of this study, our results suggested little causal effect of maternal PCOS on offspring BW. MR studies with a larger sample size of women with PCOS or more genetic instruments that would increase the variation of PCOS explained are needed in the future.

scholarly journals Birth weight, BMI in adulthood and latent autoimmune diabetes in adults: A Mendelian randomization study

2021 ◽  
Author(s):  
Yuxia Wei ◽  
Yiqiang Zhan ◽  
Josefin E. Lofvenborg ◽  
Tiinamaija Tuomi ◽  
Sofia Carlsson
Keyword(s):  
Type 2 Diabetes ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Mendelian Randomization ◽  
Autoimmune Diabetes ◽  
Sensitivity Analyses ◽  
Uk Biobank ◽  
Latent Autoimmune Diabetes ◽  
The Uk

Aims: Observational studies have found an increased risk of latent autoimmune diabetes in adults (LADA) associated with low birth weight and adult overweight/obesity. We aimed to investigate whether these associations are causal, using a two-sample Mendelian randomization (MR) design. In addition, we wanted to compare results for LADA and type 2 diabetes. Methods: We identified 129 SNPs as instrumental variables (IVs) for birth weight 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 2,634 cases and 5,947 population controls. We used the inverse-variance weighted (IVW) estimator as our primary analysis, supplemented by a series of sensitivity analyses. Results: Genetically determined birth weight was inversely associated with LADA (OR per SD [~500 g] decrease in birth weight: 2.02, 95% CI: 1.37-2.97). 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). Results persisted in a range of sensitivity analyses using other MR estimators or excluding some IVs. With respect to type 2 diabetes, the association with birth weight 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 birth weight, adult overweight/obesity, and LADA.

scholarly journals Causal Association Between Birth Weight and Atrial Fibrillation: Evidence from a Two-Sample Mendelian Randomization Analysis

2020 ◽  
Author(s):  
Songzan Chen ◽  
Fangkun Yan ◽  
Tian Xu ◽  
Yao Wang ◽  
Kaijie Zhang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Birth Weight ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Sensitivity Analyses ◽  
P Value ◽  
Causal Association ◽  
Genome Wide ◽  
A Genome ◽  
Mr Study

Abstract Background Although several observational studies have shown an association between birth weight (BW) and atrial fibrillation (AF), controversy remains. In this study, we aimed to explore the role of elevated BW on the etiology of AF. Methods A two-sample Mendelian randomization (MR) study was designed to infer the causality. The genetic data on the associations of single nucleotide polymorphisms (SNPs) with BW and AF were separately obtained from two large-scale genome-wide association study with up to 321,223 and 1,030,836 individuals respectively. SNPs were identified at a genome-wide significant level (p-value < 5 × 10− 8). The inverse variance-weighted (IVW) with fixed effects method was performed to obtain causal estimates as our primary analysis. MR-Egger regression was conducted to assess the pleiotropy and sensitivity analyses with various statistical methods were applied to evaluate the robustness of the results. Results In total, 122 SNPs were identified as the genetic instrumental variables. MR analysis revealed a causal effect of elevated BW on AF (OR = 1.21, 95% CI = 1.13–1.29, p-value = 2.39 × 10− 8). The MR-Egger regression suggested no evidence of directional pleiotropy (intercept = 0.00, p-value = 0.62). All the results in sensitivity analyses were consistent with the primary result, which confirmed the causal association between BW and AF. Conclusions The findings from the two-sample MR study indicate a causal effect of elevated BW on AF. This suggests a convenient and effective method to ease the burden of AF by reducing the number of newborns with elevated BW.

Abstract P191: Birth Weight and Risk of Hypertension: A Mendelian Randomization Study of 183433 Individuals from 60 Studies

Circulation ◽  
2019 ◽  
Vol 139 (Suppl_1) ◽  
Author(s):  
Yan Zheng ◽  
Tao Huang ◽  
Tiange Wang ◽  
Zhendong Mei ◽  
Xiang Li ◽  
...  
Keyword(s):  
Birth Weight ◽  
Mendelian Randomization
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