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Inverse relationship between a genetic risk score of 31 BMI loci and weight change before and after reaching middle age.

ABSTRACT: Genome-wide-association studies have identified numerous body mass index (BMI)-associated variants, but it is unclear how these relate to weight gain in adults at different ages.We examined the association of a genetic risk score (GRS), consisting of 31 BMI-associated variants, with an annual weight change (AWC) and a substantial weight gain (SWG) of 10% by comparing self-reported weight at 20 years (y) with baseline weight (mean: 58?y; s.d.: 8?y) in 21407 participants from the Malmö Diet and Cancer Study (MDCS), and comparing baseline weight to weight at follow-up (mean: 73?y; s.d.: 6?y) among 2673 participants. Association between GRS and AWG and SWG was replicated in 4327 GLACIER (Gene x Lifestyle interactions And Complex traits Involved in Elevated disease Risk) participants (mean: 45?y; s.d.: 7?y) with 10?y follow-up. Cohort-specific results were pooled by fixed-effect meta-analyses.In MDCS, the GRS was associated with increased AWC (?: 0.003; s.e: 0.01; P: 7 × 10(-8)) and increased odds for SWG (odds ratio (OR) 1.01 (95% confidence interval (CI): 1.00, 1.02); P: 0.013) per risk-allele from age 20y, but unexpectedly with decreased AWC (?: -0.006; s.e: 0.002; P: 0.009) and decreased odds for SWG OR 0.96 (95% CI: 0.93, 0.98); P: 0.001) between baseline and follow-up. Effect estimates from age 20?y to baseline differed significantly from those from baseline to follow-up (P: 0.0002 for AWC and P: 0.0001 for SWG). Similar to MDCS, the GRS was associated with decreased odds for SWG OR 0.98 (95% CI: 0.96, 1.00); P: 0.029) from baseline to follow-up in GLACIER. In meta-analyses (n=7000), the GRS was associated with decreased AWC (?: -0.005; s.e.m. 0.002; P: 0.002) and decreased odds for SWG OR 0.97 (95% CI: 0.96, 0.99); P: 0.001) per risk-allele.Our results provide convincing evidence for a paradoxical inversed relationship between a high number of BMI-associated risk-alleles and less weight gain during and after middle-age, in contrast to the expected increased weight gain seen in younger age.

SUBMITTER: Rukh G

PROVIDER: S-EPMC4753358 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Inverse relationship between a genetic risk score of 31 BMI loci and weight change before and after reaching middle age.

Rukh G G Ahmad S S Ericson U U Hindy G G Stocks T T Renström F F Almgren P P Nilsson P M PM Melander O O Franks P W PW Orho-Melander M M

International journal of obesity (2005) 20150916 2

<h4>Background/objective</h4>Genome-wide-association studies have identified numerous body mass index (BMI)-associated variants, but it is unclear how these relate to weight gain in adults at different ages.<h4>Methods</h4>We examined the association of a genetic risk score (GRS), consisting of 31 BMI-associated variants, with an annual weight change (AWC) and a substantial weight gain (SWG) of 10% by comparing self-reported weight at 20 years (y) with baseline weight (mean: 58 y; s.d.: 8 y) in ...[more]

PMID: 26374450

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Project description:Background:We hypothesized that increased baseline BMI and BMI change would negatively impact clinical outcomes with adjuvant breast cancer systemic therapy. Methods:Data from chemotherapy trials MA.5 and MA.21; endocrine therapy MA.12, MA.14 and MA.27; and trastuzumab HERA/MA.24 were analyzed. The primary objective was to examine the effect of BMI change on breast cancer-free interval (BCFI) landmarked at 5 years; secondary objectives included BMI changes at 1 and 3 years; BMI changes on disease-specific survival (DSS) and overall survival (OS); and effects of baseline BMI. Stratified analyses included trial therapy and composite trial stratification factors. Results:In pre-/peri-/early post-menopausal chemotherapy trials (N?=?2793), baseline BMI did not impact any endpoint and increased BMI from baseline did not significantly affect BCFI (P?=?0.85) after 5 years although it was associated with worse BCFI (P?=?0.03) and DSS (P?=?0.07) after 1 year. BMI increase by 3 and 5 years was associated with better DSS (P?=?0.01; 0.01) and OS (P?=?0.003; 0.05). In pre-menopausal endocrine therapy trial MA.12 (N?=?672), patients with higher baseline BMI had worse BCFI (P?=?0.02) after 1 year, worse DSS (P?=?0.05; 0.004) after 1 and 5 years and worse OS (P?=?0.01) after 5 years. Increased BMI did not impact BCFI (P?=?0.90) after 5 years, although it was associated with worse BCFI (P?=?0.01) after 1 year. In post-menopausal endocrine therapy trials MA.14 and MA.27 (N?=?8236), baseline BMI did not significantly impact outcome for any endpoint. BMI change did not impact BCFI or DSS after 1 or 3 years, although a mean increased BMI of 0.3 was associated with better OS (P?=?0.02) after 1 year. With the administration of trastuzumab (N?=?1395) baseline BMI and BMI change did not significantly impact outcomes. Conclusions:Higher baseline BMI and BMI increases negatively affected outcomes only in pre-/peri-/early post-menopausal trial patients. Otherwise, BMI increases similar to those expected in healthy women either did not impact outcome or were associated with better outcomes. Clinical Trials numbers:CAN-NCIC-MA5; National Cancer Institute (NCI)-V90-0027; MA.12-NCT00002542; MA.14-NCT00002864; MA.21-NCT00014222; HERA, NCT00045032;CAN-NCIC-MA24; MA-27-NCT00066573.

Dataset Information

Inverse relationship between a genetic risk score of 31 BMI loci and weight change before and after reaching middle age.

Publications

Inverse relationship between a genetic risk score of 31 BMI loci and weight change before and after reaching middle age.

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