Dataset Information

Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent.

ABSTRACT: SCOPE:Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption. METHODS AND RESULTS:A genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction <10-7) , and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3' of LINC00333) was replicated (p-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p-interaction = 7.36 × 10-8) such that each serving of low-fat dairy was associated with 0.225 kg m-2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure. CONCLUSION:Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.

SUBMITTER: Smith CE

PROVIDER: S-EPMC5803424 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent.

Smith Caren E CE Follis Jack L JL Dashti Hassan S HS Tanaka Toshiko T Graff Mariaelisa M Fretts Amanda M AM Kilpeläinen Tuomas O TO Wojczynski Mary K MK Richardson Kris K Nalls Mike A MA Schulz Christina-Alexandra CA Liu Yongmei Y Frazier-Wood Alexis C AC van Eekelen Esther E Wang Carol C de Vries Paul S PS Mikkilä Vera V Rohde Rebecca R Psaty Bruce M BM Hansen Torben T Feitosa Mary F MF Lai Chao-Qiang CQ Houston Denise K DK Ferruci Luigi L Ericson Ulrika U Wang Zhe Z de Mutsert Renée R Oddy Wendy H WH de Jonge Ester A L EAL Seppälä Ilkka I Justice Anne E AE Lemaitre Rozenn N RN Sørensen Thorkild I A TIA Province Michael A MA Parnell Laurence D LD Garcia Melissa E ME Bandinelli Stefania S Orho-Melander Marju M Rich Stephen S SS Rosendaal Frits R FR Pennell Craig E CE Kiefte-de Jong Jessica C JC Kähönen Mika M Young Kristin L KL Pedersen Oluf O Aslibekyan Stella S Rotter Jerome I JI Mook-Kanamori Dennis O DO Zillikens M Carola MC Raitakari Olli T OT North Kari E KE Overvad Kim K Arnett Donna K DK Hofman Albert A Lehtimäki Terho T Tjønneland Anne A Uitterlinden André G AG Rivadeneira Fernando F Franco Oscar H OH German J Bruce JB Siscovick David S DS Cupples L Adrienne LA Ordovás José M JM

Molecular nutrition & food research 20171211 3

<h4>Scope</h4>Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption.<h4>Methods and results</h4>A genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) w ...[more]

PMID: 28941034

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Project description:BACKGROUND:Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. METHODS:We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases? = ?46,325, controls? = ?42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. RESULTS:In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR]? = ?0.65 per 5 kg/m2 increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32?×?10-10). The associations were similar for both premenopausal (OR?? = ??0.44, 95% CI:0.31-0.62, p? = ?9.91?×?10-8) and postmenopausal breast cancer (OR? = ?0.57, 95%?CI: 0.46-0.71, p? = ?1.88?×?10-8). This association was replicated in the data from the DRIVE consortium (OR? = ?0.72, 95%?CI: 0.60-0.84, p?? = ??1.64?×?10-7). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p?<?0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. CONCLUSIONS:BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.

Project description:BackgroundObesity and diabetes mellitus (DM) are public health concerns in Mexico of top-level priority due to their high prevalence and their growth rate in recent decades. The accumulation of adipose tissue leads to an unbalanced release of pro-oxidant factors, which causes cellular damage and favors the development of comorbidities. Recent evidence suggests that oxidative stress also promotes the accumulation of adipose tissue and the development of insulin resistance. The objective of this study is to evaluate the association between usual intake of antioxidant nutrients, specifically vitamins A, C, E and magnesium with body mass index (BMI), waist circumference (WC) and serum glucose concentrations in a representative sample of Mexican adults.MethodologyWe analyzed data on diet, BMI, WC and serum glucose from the Mexican National Health and Nutrition Survey 2012. Analysis included 20- to 65-year-old adults without a known diagnosis of DM (n = 1573). Dietary information was obtained using the five-step multiple-pass method developed by the United States Department of Agriculture and adapted to the Mexican context. Nutrient usual intake distributions were estimated using the Iowa State University method, through the "Software for Intake Distribution Estimation" (PC-Side) v.1.02. Associations were analyzed using multivariate regression models.ResultsHigher dietary magnesium intake was associated with lower markers of adiposity, so that an increase in 10 mg per 1000 kcal/day of magnesium was associated with an average decrease in BMI of 0.72% (95% CI: -1.36, - 0.08) and 0.49 cm (95% CI: -0.92, - 0.07) of WC. Additionally, in women with normal glucose concentrations, an increase in magnesium intake was associated with an average decrease in serum glucose by 0.59% (95% CI: -1.08, - 0.09).ConclusionThe results suggest that magnesium intake is associated with lower BMI, WC and serum glucose in Mexican population. However, more studies are required to elucidate the nature of this association.

Dataset Information

Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent.

Publications

Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent.

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