Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE consortium studies1-4

Adela Hruby, Julius S. Ngwa, Frida Renström, Mary K. Mary, Andrea Ganna, Göran Hallmans, Denise K. Houston, Paul F. Jacques, Stavroula Kanoni, Terho Lehtimäki, Rozenn N. Lemaitre, Ani Manichaikul, Kari E. North, Ioanna Ntalla, Emily Sonestedt, Toshiko Tanaka, Frank J A van Rooij, Stefania Bandinelli, Luc Djoussé, Efi Grigoriou & 39 others Ingegerd Johansson, Kurt K. Lohman, James S. Pankow, Olli T. Raitakari, Ulf Riserus, Mary Yannakoulia, M. Carola Zillikens, Neelam Hassanali, Yongmei Liu, Dariush Mozaffarian, Constantina Papoutsakis, Ann Christine Syvänen, André G. Uitterlinden, Jorma Viikari, Christopher J. Groves, Albert Hofman Lind, Lars Lind, Mark I. McCarthy, Vera Mikkilä̈, Kenneth Mukamal, Oscar H. Franco, Ingrid B. Borecki, L. Adrienne Cupples, George V. Dedoussis, Luigi Ferrucci, Frank B. Hu, Erik Ingelsson, Mika Kähönen, W. H Linda Kao, Stephen B. Kritchevsky, Marju Orho-Melander, Inga Prokopenko, Jerome I. Rotter, David S. Siscovick, Jacqueline C M Witteman, Paul W. Franks, James B. Meigs, Nicola M. McKeown, Jennifer A. Nettleton

Research output: Contribution to journalArticle

Abstract

Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesiumintake and fasting glucose and insulin. Fifteen studies fromthe CHARGE (Cohorts for Heart and Aging Research inGenomic Epidemiology) Consortiumprovided data fromup to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = 20.009 mmol/L (95% CI: 20.013, 20.005), P <0.0001] and insulin [20.020 ln-pmol/L (95%CI:20.024,20.017), P <0.0001].Nomagnesium-related SNP or interaction between any SNP andmagnesiumreached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.

Original languageEnglish (US)
Pages (from-to)345-353
Number of pages9
JournalJournal of Nutrition
Volume143
Issue number3
DOIs
StatePublished - Mar 2013
Externally publishedYes

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Genetic Loci
Magnesium
Meta-Analysis
Fasting
Epidemiology
Insulin
Glucose
Single Nucleotide Polymorphism
Research
Energy Intake
Observational Studies
Cohort Studies

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE consortium studies1-4 . / Hruby, Adela; Ngwa, Julius S.; Renström, Frida; Mary, Mary K.; Ganna, Andrea; Hallmans, Göran; Houston, Denise K.; Jacques, Paul F.; Kanoni, Stavroula; Lehtimäki, Terho; Lemaitre, Rozenn N.; Manichaikul, Ani; North, Kari E.; Ntalla, Ioanna; Sonestedt, Emily; Tanaka, Toshiko; van Rooij, Frank J A; Bandinelli, Stefania; Djoussé, Luc; Grigoriou, Efi; Johansson, Ingegerd; Lohman, Kurt K.; Pankow, James S.; Raitakari, Olli T.; Riserus, Ulf; Yannakoulia, Mary; Zillikens, M. Carola; Hassanali, Neelam; Liu, Yongmei; Mozaffarian, Dariush; Papoutsakis, Constantina; Syvänen, Ann Christine; Uitterlinden, André G.; Viikari, Jorma; Groves, Christopher J.; Lind, Albert Hofman; Lind, Lars; McCarthy, Mark I.; Mikkilä̈, Vera; Mukamal, Kenneth; Franco, Oscar H.; Borecki, Ingrid B.; Cupples, L. Adrienne; Dedoussis, George V.; Ferrucci, Luigi; Hu, Frank B.; Ingelsson, Erik; Kähönen, Mika; Kao, W. H Linda; Kritchevsky, Stephen B.; Orho-Melander, Marju; Prokopenko, Inga; Rotter, Jerome I.; Siscovick, David S.; Witteman, Jacqueline C M; Franks, Paul W.; Meigs, James B.; McKeown, Nicola M.; Nettleton, Jennifer A.

In: Journal of Nutrition, Vol. 143, No. 3, 03.2013, p. 345-353.

Research output: Contribution to journalArticle

Hruby, A, Ngwa, JS, Renström, F, Mary, MK, Ganna, A, Hallmans, G, Houston, DK, Jacques, PF, Kanoni, S, Lehtimäki, T, Lemaitre, RN, Manichaikul, A, North, KE, Ntalla, I, Sonestedt, E, Tanaka, T, van Rooij, FJA, Bandinelli, S, Djoussé, L, Grigoriou, E, Johansson, I, Lohman, KK, Pankow, JS, Raitakari, OT, Riserus, U, Yannakoulia, M, Zillikens, MC, Hassanali, N, Liu, Y, Mozaffarian, D, Papoutsakis, C, Syvänen, AC, Uitterlinden, AG, Viikari, J, Groves, CJ, Lind, AH, Lind, L, McCarthy, MI, Mikkilä̈, V, Mukamal, K, Franco, OH, Borecki, IB, Cupples, LA, Dedoussis, GV, Ferrucci, L, Hu, FB, Ingelsson, E, Kähönen, M, Kao, WHL, Kritchevsky, SB, Orho-Melander, M, Prokopenko, I, Rotter, JI, Siscovick, DS, Witteman, JCM, Franks, PW, Meigs, JB, McKeown, NM & Nettleton, JA 2013, 'Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE consortium studies1-4 ', Journal of Nutrition, vol. 143, no. 3, pp. 345-353. https://doi.org/10.3945/jn.112.172049
Hruby, Adela ; Ngwa, Julius S. ; Renström, Frida ; Mary, Mary K. ; Ganna, Andrea ; Hallmans, Göran ; Houston, Denise K. ; Jacques, Paul F. ; Kanoni, Stavroula ; Lehtimäki, Terho ; Lemaitre, Rozenn N. ; Manichaikul, Ani ; North, Kari E. ; Ntalla, Ioanna ; Sonestedt, Emily ; Tanaka, Toshiko ; van Rooij, Frank J A ; Bandinelli, Stefania ; Djoussé, Luc ; Grigoriou, Efi ; Johansson, Ingegerd ; Lohman, Kurt K. ; Pankow, James S. ; Raitakari, Olli T. ; Riserus, Ulf ; Yannakoulia, Mary ; Zillikens, M. Carola ; Hassanali, Neelam ; Liu, Yongmei ; Mozaffarian, Dariush ; Papoutsakis, Constantina ; Syvänen, Ann Christine ; Uitterlinden, André G. ; Viikari, Jorma ; Groves, Christopher J. ; Lind, Albert Hofman ; Lind, Lars ; McCarthy, Mark I. ; Mikkilä̈, Vera ; Mukamal, Kenneth ; Franco, Oscar H. ; Borecki, Ingrid B. ; Cupples, L. Adrienne ; Dedoussis, George V. ; Ferrucci, Luigi ; Hu, Frank B. ; Ingelsson, Erik ; Kähönen, Mika ; Kao, W. H Linda ; Kritchevsky, Stephen B. ; Orho-Melander, Marju ; Prokopenko, Inga ; Rotter, Jerome I. ; Siscovick, David S. ; Witteman, Jacqueline C M ; Franks, Paul W. ; Meigs, James B. ; McKeown, Nicola M. ; Nettleton, Jennifer A. / Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE consortium studies1-4 In: Journal of Nutrition. 2013 ; Vol. 143, No. 3. pp. 345-353.
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abstract = "Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesiumintake and fasting glucose and insulin. Fifteen studies fromthe CHARGE (Cohorts for Heart and Aging Research inGenomic Epidemiology) Consortiumprovided data fromup to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = 20.009 mmol/L (95{\%} CI: 20.013, 20.005), P <0.0001] and insulin [20.020 ln-pmol/L (95{\%}CI:20.024,20.017), P <0.0001].Nomagnesium-related SNP or interaction between any SNP andmagnesiumreached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.",
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T1 - Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE consortium studies1-4

AU - Hruby, Adela

AU - Ngwa, Julius S.

AU - Renström, Frida

AU - Mary, Mary K.

AU - Ganna, Andrea

AU - Hallmans, Göran

AU - Houston, Denise K.

AU - Jacques, Paul F.

AU - Kanoni, Stavroula

AU - Lehtimäki, Terho

AU - Lemaitre, Rozenn N.

AU - Manichaikul, Ani

AU - North, Kari E.

AU - Ntalla, Ioanna

AU - Sonestedt, Emily

AU - Tanaka, Toshiko

AU - van Rooij, Frank J A

AU - Bandinelli, Stefania

AU - Djoussé, Luc

AU - Grigoriou, Efi

AU - Johansson, Ingegerd

AU - Lohman, Kurt K.

AU - Pankow, James S.

AU - Raitakari, Olli T.

AU - Riserus, Ulf

AU - Yannakoulia, Mary

AU - Zillikens, M. Carola

AU - Hassanali, Neelam

AU - Liu, Yongmei

AU - Mozaffarian, Dariush

AU - Papoutsakis, Constantina

AU - Syvänen, Ann Christine

AU - Uitterlinden, André G.

AU - Viikari, Jorma

AU - Groves, Christopher J.

AU - Lind, Albert Hofman

AU - Lind, Lars

AU - McCarthy, Mark I.

AU - Mikkilä̈, Vera

AU - Mukamal, Kenneth

AU - Franco, Oscar H.

AU - Borecki, Ingrid B.

AU - Cupples, L. Adrienne

AU - Dedoussis, George V.

AU - Ferrucci, Luigi

AU - Hu, Frank B.

AU - Ingelsson, Erik

AU - Kähönen, Mika

AU - Kao, W. H Linda

AU - Kritchevsky, Stephen B.

AU - Orho-Melander, Marju

AU - Prokopenko, Inga

AU - Rotter, Jerome I.

AU - Siscovick, David S.

AU - Witteman, Jacqueline C M

AU - Franks, Paul W.

AU - Meigs, James B.

AU - McKeown, Nicola M.

AU - Nettleton, Jennifer A.

PY - 2013/3

Y1 - 2013/3

N2 - Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesiumintake and fasting glucose and insulin. Fifteen studies fromthe CHARGE (Cohorts for Heart and Aging Research inGenomic Epidemiology) Consortiumprovided data fromup to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = 20.009 mmol/L (95% CI: 20.013, 20.005), P <0.0001] and insulin [20.020 ln-pmol/L (95%CI:20.024,20.017), P <0.0001].Nomagnesium-related SNP or interaction between any SNP andmagnesiumreached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.

AB - Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesiumintake and fasting glucose and insulin. Fifteen studies fromthe CHARGE (Cohorts for Heart and Aging Research inGenomic Epidemiology) Consortiumprovided data fromup to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = 20.009 mmol/L (95% CI: 20.013, 20.005), P <0.0001] and insulin [20.020 ln-pmol/L (95%CI:20.024,20.017), P <0.0001].Nomagnesium-related SNP or interaction between any SNP andmagnesiumreached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.

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