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Genetic determinants of serum vitamin B12 and their relation to body mass index.

ABSTRACT: Lower serum vitamin B12 levels have been related to adverse metabolic health profiles, including adiposity. We used a Mendelian randomization design to test whether this relation might be causal. We included two Danish population-based studies (ntotal = 9311). Linear regression was used to test for associations between (1) serum vitamin B12 levels and body mass index (BMI), (2) genetic variants and serum vitamin B12 levels, and (3) genetic variants and BMI. The effect of a genetically determined decrease in serum vitamin B12 on BMI was estimated by instrumental variable regression. Decreased serum vitamin B12 associated with increased BMI (P < 1 × 10-4). A genetic risk score based on eight vitamin B12 associated variants associated strongly with serum vitamin B12 (P < 2 × 10-43), but not with BMI (P = 0.91). Instrumental variable regression showed that a 20% decrease in serum vitamin B12 was associated with a 0.09 kg/m2 (95% CI 0.05; 0.13) increase in BMI (P = 3 × 10-5), whereas a genetically induced 20% decrease in serum vitamin B12 had no effect on BMI [-0.03 (95% CI -0.22; 0.16) kg/m2] (P = 0.74). Nevertheless, the strongest serum vitamin B12 variant, FUT2 rs602662, which was excluded from the B12 genetic risk score due to potential pleiotropic effects, showed a per allele effect of 0.15 kg/m2 (95% CI 0.01; 0.32) on BMI (P = 0.03). This association was accentuated including two German cohorts (ntotal = 5050), with a combined effect of 0.19 kg/m2 (95% CI 0.08; 0.30) (P = 4 × 10-4). We found no support for a causal role of decreased serum vitamin B12 levels in obesity. However, our study suggests that FUT2, through its regulation of the cross-talk between gut microbes and the human host, might explain a part of the observational association between serum vitamin B12 and BMI.

SUBMITTER: Allin KH

PROVIDER: S-EPMC5374184 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Genetic determinants of serum vitamin B12 and their relation to body mass index.

Allin Kristine H KH Friedrich Nele N Pietzner Maik M Grarup Niels N Thuesen Betina H BH Linneberg Allan A Pisinger Charlotta C Hansen Torben T Pedersen Oluf O Sandholt Camilla H CH

European journal of epidemiology 20161219 2

Lower serum vitamin B12 levels have been related to adverse metabolic health profiles, including adiposity. We used a Mendelian randomization design to test whether this relation might be causal. We included two Danish population-based studies (n<sub>total</sub> = 9311). Linear regression was used to test for associations between (1) serum vitamin B12 levels and body mass index (BMI), (2) genetic variants and serum vitamin B12 levels, and (3) genetic variants and BMI. The effect of a genetically ...[more]

PMID: 27995393

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Project description:BackgroundPregestational excessive body mass index (BMI) is linked to an increased risk for gestational diabetes mellitus (GDM), but less is known on the effect of adolescent BMI on GDM occurrence. The study aimed to investigate possible associations of adolescent BMI and changes in BMI experienced before first pregnancy, with gestational diabetes risk.MethodsThis retrospective study was based on linkage of a military screening database of adolescent health status (Israel Defence Forces) including measured height and weight, with medical records (Maccabi Healthcare Services, MHS) of a state-mandated health provider. The latter covers about 25% of the Israeli population; about 90% of pregnant women undergo screening by the two-step Carpenter-Coustan method. Adolescent BMI was categorized according to Center of Disease Control and Prevention percentiles. Only first documented pregnanies were analyzed and GDM was the outcome.FindingsOf 190,905 nulliparous women, 10,265 (5.4%) developed GDM. Incidence proportions of GDM were 5.1%, 6.1%, 7.3%, and 8.9% among women with adolescent normal BMI, underweight, overweight, and obesity (p<0.001), respectively. In models that accounted for age at pregnancy, birth year, and sociodemographic variables, the adjusted odd ratios (aORs) for developing GDM were: 1.2 (95%CI, 1.1-1.3), 1.5 (1.4-1.6), and 1.9 (1.7-2.1) for adolescent underweight, overweight, and obesity (reference group, normal BMI). Adolescent BMI tracked with BMI notes in the pre-pregnancy period (r=63%). Resuming normal pre-pregnancy BMI from overweight or obesity in adolescence diminished GDM risk, but this diminished risk was not observed among those who returned to a normal per-pre-pregnancy BMI from being underweight in adolescence. Sustained overweight or obesity conferred an aOR for developing GDM of 2.5 (2.2-2.7); weight gain from adolescent underweight and normal BMI to pre-pregnancy excessive BMI conferred aORs of 3.1 (1.6-6.2) and 2.6 (2.2-2.7), respectively.InterpretationChange in BMI status from adolescence to pre-pregnancy may contribute to GDM risk. Identifying at-risk populations is important for early preventive interventions.FundingNone.

Dataset Information

Genetic determinants of serum vitamin B12 and their relation to body mass index.

Publications

Genetic determinants of serum vitamin B12 and their relation to body mass index.

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