Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

Janine F. Felix, Jonathan P. Bradfield, Claire Monnereau, Ralf J P Van Der Valk, Evie Stergiakouli, Alessandra Chesi, Romy Gaillard, Bjarke Feenstra, Elisabeth Thiering, Eskil Kreiner-Møller, Anubha Mahajan, Pitkänen Niina Pitkänen, Raimo Joro, Alana Cavadino, Ville Huikari, Steve Franks, Maria M. Groen-Blokhuis, Diana L. Cousminer, Julie A. Marsh, Terho Lehtimäki & 97 others John A. Curtin, Jesus Vioque, Tarunveer S. Ahluwalia, Ronny Myhre, Thomas S. Price, Vilor-Tejedor Natalia Vilor-Tejedor, Loïc Yengo, Niels Grarup, Ioanna Ntalla, Wei Ang, Mustafa Atalay, Hans Bisgaard, Alexandra I. Blakemore, Amelie Bonnefond, Lisbeth Carstensen, Johan Eriksson, Claudia Flexeder, Lude Franke, Frank Geller, Mandy Geserick, Anna Liisa Hartikainen, Claire M A Haworth, Joel N. Hirschhorn, Albert Hofman, Jens Christian Holm, Momoko Horikoshi, Jouke Jan Hottenga, Jinyan Huang, Haja N. Kadarmideen, Mika Kähönen, Wieland Kiess, Hanna Maaria Lakka, Timo A. Lakka, Alexandra M. Lewin, Liming Liang, Leo Pekka Lyytikäinen, Baoshan Ma, Per Magnus, Shana E. McCormack, George McMahon, Frank D. Mentch, Christel M. Middeldorp, Clare S. Murray, Katja Pahkala, Tune H. Pers, Roland Pfäffle, Dirkje S. Postma, Christine Power, Angela Simpson, Verena Sengpiel, Carla M T Tiesler, Maties Torrent, André G. Uitterlinden, Joyce B. Van Meurs, Rebecca Vinding, Johannes Waage, Jane Wardle, Eleftheria Zeggini, Babette S. Zemel, George V. Dedoussis, Oluf Pedersen, Philippe Froguel, Jordi Sunyer, Robert Plomin, Bo Jacobsson, Torben Hansen, Juan R. Gonzalez, Adnan Custovic, Olli T. Raitakari, Craig E. Pennell, Widén Elisabeth Widén, Dorret I. Boomsma, Gerard H. Koppelman, Sylvain Sebert, Marjo Riitta Järvelin, Elina Hyppönen, Mark I. McCarthy, Virpi Lindi, Niinikoski Harri, Antje Körner, Klaus Bønnelykke, Joachim Heinrich, Mads Melbye, Fernando Rivadeneira, Hakon Hakonarson, Susan M. Ring, George Davey Smith, Thorkild I A Sørensen, Nicholas J. Timpson, Struan F A Grant, Vincent W V Jaddoe, Heidi J. Kalkwarf, Joan M. Lappe, Vicente Gilsanz, Sharon E. Oberfield, John A. Shepherd, Andrea Kelly

    Research output: Contribution to journalArticle

    100 Citations (Scopus)

    Abstract

    A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown.We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores.We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value -8) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10-10) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.

    Original languageEnglish
    Article numberddv472
    Pages (from-to)389-403
    Number of pages15
    JournalHuman Molecular Genetics
    Volume25
    Issue number2
    Early online date24 Nov 2015
    DOIs
    Publication statusPublished - 15 Jan 2016

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    Genome-Wide Association Study
    Body Mass Index
    Alleles
    Genetic Loci
    Pediatric Obesity
    Single Nucleotide Polymorphism
    Meta-Analysis
    Joints
    Genome

    Cite this

    Felix, J. F., Bradfield, J. P., Monnereau, C., Van Der Valk, R. J. P., Stergiakouli, E., Chesi, A., ... Kelly, A. (2016). Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. Human Molecular Genetics, 25(2), 389-403. [ddv472]. https://doi.org/10.1093/hmg/ddv472, https://doi.org/10.1093/hmg/ddv472
    Felix, Janine F. ; Bradfield, Jonathan P. ; Monnereau, Claire ; Van Der Valk, Ralf J P ; Stergiakouli, Evie ; Chesi, Alessandra ; Gaillard, Romy ; Feenstra, Bjarke ; Thiering, Elisabeth ; Kreiner-Møller, Eskil ; Mahajan, Anubha ; Niina Pitkänen, Pitkänen ; Joro, Raimo ; Cavadino, Alana ; Huikari, Ville ; Franks, Steve ; Groen-Blokhuis, Maria M. ; Cousminer, Diana L. ; Marsh, Julie A. ; Lehtimäki, Terho ; Curtin, John A. ; Vioque, Jesus ; Ahluwalia, Tarunveer S. ; Myhre, Ronny ; Price, Thomas S. ; Natalia Vilor-Tejedor, Vilor-Tejedor ; Yengo, Loïc ; Grarup, Niels ; Ntalla, Ioanna ; Ang, Wei ; Atalay, Mustafa ; Bisgaard, Hans ; Blakemore, Alexandra I. ; Bonnefond, Amelie ; Carstensen, Lisbeth ; Eriksson, Johan ; Flexeder, Claudia ; Franke, Lude ; Geller, Frank ; Geserick, Mandy ; Hartikainen, Anna Liisa ; Haworth, Claire M A ; Hirschhorn, Joel N. ; Hofman, Albert ; Holm, Jens Christian ; Horikoshi, Momoko ; Hottenga, Jouke Jan ; Huang, Jinyan ; Kadarmideen, Haja N. ; Kähönen, Mika ; Kiess, Wieland ; Lakka, Hanna Maaria ; Lakka, Timo A. ; Lewin, Alexandra M. ; Liang, Liming ; Lyytikäinen, Leo Pekka ; Ma, Baoshan ; Magnus, Per ; McCormack, Shana E. ; McMahon, George ; Mentch, Frank D. ; Middeldorp, Christel M. ; Murray, Clare S. ; Pahkala, Katja ; Pers, Tune H. ; Pfäffle, Roland ; Postma, Dirkje S. ; Power, Christine ; Simpson, Angela ; Sengpiel, Verena ; Tiesler, Carla M T ; Torrent, Maties ; Uitterlinden, André G. ; Van Meurs, Joyce B. ; Vinding, Rebecca ; Waage, Johannes ; Wardle, Jane ; Zeggini, Eleftheria ; Zemel, Babette S. ; Dedoussis, George V. ; Pedersen, Oluf ; Froguel, Philippe ; Sunyer, Jordi ; Plomin, Robert ; Jacobsson, Bo ; Hansen, Torben ; Gonzalez, Juan R. ; Custovic, Adnan ; Raitakari, Olli T. ; Pennell, Craig E. ; Elisabeth Widén, Widén ; Boomsma, Dorret I. ; Koppelman, Gerard H. ; Sebert, Sylvain ; Järvelin, Marjo Riitta ; Hyppönen, Elina ; McCarthy, Mark I. ; Lindi, Virpi ; Harri, Niinikoski ; Körner, Antje ; Bønnelykke, Klaus ; Heinrich, Joachim ; Melbye, Mads ; Rivadeneira, Fernando ; Hakonarson, Hakon ; Ring, Susan M. ; Smith, George Davey ; Sørensen, Thorkild I A ; Timpson, Nicholas J. ; Grant, Struan F A ; Jaddoe, Vincent W V ; Kalkwarf, Heidi J. ; Lappe, Joan M. ; Gilsanz, Vicente ; Oberfield, Sharon E. ; Shepherd, John A. ; Kelly, Andrea. / Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. In: Human Molecular Genetics. 2016 ; Vol. 25, No. 2. pp. 389-403.
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    title = "Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index",
    abstract = "A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown.We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores.We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value -8) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10-10) increase in childhood body mass index in a population of 1955 children. This risk score explained 2{\%} of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.",
    author = "Felix, {Janine F.} and Bradfield, {Jonathan P.} and Claire Monnereau and {Van Der Valk}, {Ralf J P} and Evie Stergiakouli and Alessandra Chesi and Romy Gaillard and Bjarke Feenstra and Elisabeth Thiering and Eskil Kreiner-M{\o}ller and Anubha Mahajan and {Niina Pitk{\"a}nen}, Pitk{\"a}nen and Raimo Joro and Alana Cavadino and Ville Huikari and Steve Franks and Groen-Blokhuis, {Maria M.} and Cousminer, {Diana L.} and Marsh, {Julie A.} and Terho Lehtim{\"a}ki and Curtin, {John A.} and Jesus Vioque and Ahluwalia, {Tarunveer S.} and Ronny Myhre and Price, {Thomas S.} and {Natalia Vilor-Tejedor}, Vilor-Tejedor and Lo{\"i}c Yengo and Niels Grarup and Ioanna Ntalla and Wei Ang and Mustafa Atalay and Hans Bisgaard and Blakemore, {Alexandra I.} and Amelie Bonnefond and Lisbeth Carstensen and Johan Eriksson and Claudia Flexeder and Lude Franke and Frank Geller and Mandy Geserick and Hartikainen, {Anna Liisa} and Haworth, {Claire M A} and Hirschhorn, {Joel N.} and Albert Hofman and Holm, {Jens Christian} and Momoko Horikoshi and Hottenga, {Jouke Jan} and Jinyan Huang and Kadarmideen, {Haja N.} and Mika K{\"a}h{\"o}nen and Wieland Kiess and Lakka, {Hanna Maaria} and Lakka, {Timo A.} and Lewin, {Alexandra M.} and Liming Liang and Lyytik{\"a}inen, {Leo Pekka} and Baoshan Ma and Per Magnus and McCormack, {Shana E.} and George McMahon and Mentch, {Frank D.} and Middeldorp, {Christel M.} and Murray, {Clare S.} and Katja Pahkala and Pers, {Tune H.} and Roland Pf{\"a}ffle and Postma, {Dirkje S.} and Christine Power and Angela Simpson and Verena Sengpiel and Tiesler, {Carla M T} and Maties Torrent and Uitterlinden, {Andr{\'e} G.} and {Van Meurs}, {Joyce B.} and Rebecca Vinding and Johannes Waage and Jane Wardle and Eleftheria Zeggini and Zemel, {Babette S.} and Dedoussis, {George V.} and Oluf Pedersen and Philippe Froguel and Jordi Sunyer and Robert Plomin and Bo Jacobsson and Torben Hansen and Gonzalez, {Juan R.} and Adnan Custovic and Raitakari, {Olli T.} and Pennell, {Craig E.} and {Elisabeth Wid{\'e}n}, Wid{\'e}n and Boomsma, {Dorret I.} and Koppelman, {Gerard H.} and Sylvain Sebert and J{\"a}rvelin, {Marjo Riitta} and Elina Hypp{\"o}nen and McCarthy, {Mark I.} and Virpi Lindi and Niinikoski Harri and Antje K{\"o}rner and Klaus B{\o}nnelykke and Joachim Heinrich and Mads Melbye and Fernando Rivadeneira and Hakon Hakonarson and Ring, {Susan M.} and Smith, {George Davey} and S{\o}rensen, {Thorkild I A} and Timpson, {Nicholas J.} and Grant, {Struan F A} and Jaddoe, {Vincent W V} and Kalkwarf, {Heidi J.} and Lappe, {Joan M.} and Vicente Gilsanz and Oberfield, {Sharon E.} and Shepherd, {John A.} and Andrea Kelly",
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    doi = "10.1093/hmg/ddv472",
    language = "English",
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    pages = "389--403",
    journal = "Human Molecular Genetics",
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    publisher = "OXFORD UNIV PRESS UNITED KINGDOM",
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    Felix, JF, Bradfield, JP, Monnereau, C, Van Der Valk, RJP, Stergiakouli, E, Chesi, A, Gaillard, R, Feenstra, B, Thiering, E, Kreiner-Møller, E, Mahajan, A, Niina Pitkänen, P, Joro, R, Cavadino, A, Huikari, V, Franks, S, Groen-Blokhuis, MM, Cousminer, DL, Marsh, JA, Lehtimäki, T, Curtin, JA, Vioque, J, Ahluwalia, TS, Myhre, R, Price, TS, Natalia Vilor-Tejedor, V-T, Yengo, L, Grarup, N, Ntalla, I, Ang, W, Atalay, M, Bisgaard, H, Blakemore, AI, Bonnefond, A, Carstensen, L, Eriksson, J, Flexeder, C, Franke, L, Geller, F, Geserick, M, Hartikainen, AL, Haworth, CMA, Hirschhorn, JN, Hofman, A, Holm, JC, Horikoshi, M, Hottenga, JJ, Huang, J, Kadarmideen, HN, Kähönen, M, Kiess, W, Lakka, HM, Lakka, TA, Lewin, AM, Liang, L, Lyytikäinen, LP, Ma, B, Magnus, P, McCormack, SE, McMahon, G, Mentch, FD, Middeldorp, CM, Murray, CS, Pahkala, K, Pers, TH, Pfäffle, R, Postma, DS, Power, C, Simpson, A, Sengpiel, V, Tiesler, CMT, Torrent, M, Uitterlinden, AG, Van Meurs, JB, Vinding, R, Waage, J, Wardle, J, Zeggini, E, Zemel, BS, Dedoussis, GV, Pedersen, O, Froguel, P, Sunyer, J, Plomin, R, Jacobsson, B, Hansen, T, Gonzalez, JR, Custovic, A, Raitakari, OT, Pennell, CE, Elisabeth Widén, W, Boomsma, DI, Koppelman, GH, Sebert, S, Järvelin, MR, Hyppönen, E, McCarthy, MI, Lindi, V, Harri, N, Körner, A, Bønnelykke, K, Heinrich, J, Melbye, M, Rivadeneira, F, Hakonarson, H, Ring, SM, Smith, GD, Sørensen, TIA, Timpson, NJ, Grant, SFA, Jaddoe, VWV, Kalkwarf, HJ, Lappe, JM, Gilsanz, V, Oberfield, SE, Shepherd, JA & Kelly, A 2016, 'Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index' Human Molecular Genetics, vol. 25, no. 2, ddv472, pp. 389-403. https://doi.org/10.1093/hmg/ddv472, https://doi.org/10.1093/hmg/ddv472

    Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. / Felix, Janine F.; Bradfield, Jonathan P.; Monnereau, Claire; Van Der Valk, Ralf J P; Stergiakouli, Evie; Chesi, Alessandra; Gaillard, Romy; Feenstra, Bjarke; Thiering, Elisabeth; Kreiner-Møller, Eskil; Mahajan, Anubha; Niina Pitkänen, Pitkänen; Joro, Raimo; Cavadino, Alana; Huikari, Ville; Franks, Steve; Groen-Blokhuis, Maria M.; Cousminer, Diana L.; Marsh, Julie A.; Lehtimäki, Terho; Curtin, John A.; Vioque, Jesus; Ahluwalia, Tarunveer S.; Myhre, Ronny; Price, Thomas S.; Natalia Vilor-Tejedor, Vilor-Tejedor; Yengo, Loïc; Grarup, Niels; Ntalla, Ioanna; Ang, Wei; Atalay, Mustafa; Bisgaard, Hans; Blakemore, Alexandra I.; Bonnefond, Amelie; Carstensen, Lisbeth; Eriksson, Johan; Flexeder, Claudia; Franke, Lude; Geller, Frank; Geserick, Mandy; Hartikainen, Anna Liisa; Haworth, Claire M A; Hirschhorn, Joel N.; Hofman, Albert; Holm, Jens Christian; Horikoshi, Momoko; Hottenga, Jouke Jan; Huang, Jinyan; Kadarmideen, Haja N.; Kähönen, Mika; Kiess, Wieland; Lakka, Hanna Maaria; Lakka, Timo A.; Lewin, Alexandra M.; Liang, Liming; Lyytikäinen, Leo Pekka; Ma, Baoshan; Magnus, Per; McCormack, Shana E.; McMahon, George; Mentch, Frank D.; Middeldorp, Christel M.; Murray, Clare S.; Pahkala, Katja; Pers, Tune H.; Pfäffle, Roland; Postma, Dirkje S.; Power, Christine; Simpson, Angela; Sengpiel, Verena; Tiesler, Carla M T; Torrent, Maties; Uitterlinden, André G.; Van Meurs, Joyce B.; Vinding, Rebecca; Waage, Johannes; Wardle, Jane; Zeggini, Eleftheria; Zemel, Babette S.; Dedoussis, George V.; Pedersen, Oluf; Froguel, Philippe; Sunyer, Jordi; Plomin, Robert; Jacobsson, Bo; Hansen, Torben; Gonzalez, Juan R.; Custovic, Adnan; Raitakari, Olli T.; Pennell, Craig E.; Elisabeth Widén, Widén; Boomsma, Dorret I.; Koppelman, Gerard H.; Sebert, Sylvain; Järvelin, Marjo Riitta; Hyppönen, Elina; McCarthy, Mark I.; Lindi, Virpi; Harri, Niinikoski; Körner, Antje; Bønnelykke, Klaus; Heinrich, Joachim; Melbye, Mads; Rivadeneira, Fernando; Hakonarson, Hakon; Ring, Susan M.; Smith, George Davey; Sørensen, Thorkild I A; Timpson, Nicholas J.; Grant, Struan F A; Jaddoe, Vincent W V; Kalkwarf, Heidi J.; Lappe, Joan M.; Gilsanz, Vicente; Oberfield, Sharon E.; Shepherd, John A.; Kelly, Andrea.

    In: Human Molecular Genetics, Vol. 25, No. 2, ddv472, 15.01.2016, p. 389-403.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

    AU - Felix, Janine F.

    AU - Bradfield, Jonathan P.

    AU - Monnereau, Claire

    AU - Van Der Valk, Ralf J P

    AU - Stergiakouli, Evie

    AU - Chesi, Alessandra

    AU - Gaillard, Romy

    AU - Feenstra, Bjarke

    AU - Thiering, Elisabeth

    AU - Kreiner-Møller, Eskil

    AU - Mahajan, Anubha

    AU - Niina Pitkänen, Pitkänen

    AU - Joro, Raimo

    AU - Cavadino, Alana

    AU - Huikari, Ville

    AU - Franks, Steve

    AU - Groen-Blokhuis, Maria M.

    AU - Cousminer, Diana L.

    AU - Marsh, Julie A.

    AU - Lehtimäki, Terho

    AU - Curtin, John A.

    AU - Vioque, Jesus

    AU - Ahluwalia, Tarunveer S.

    AU - Myhre, Ronny

    AU - Price, Thomas S.

    AU - Natalia Vilor-Tejedor, Vilor-Tejedor

    AU - Yengo, Loïc

    AU - Grarup, Niels

    AU - Ntalla, Ioanna

    AU - Ang, Wei

    AU - Atalay, Mustafa

    AU - Bisgaard, Hans

    AU - Blakemore, Alexandra I.

    AU - Bonnefond, Amelie

    AU - Carstensen, Lisbeth

    AU - Eriksson, Johan

    AU - Flexeder, Claudia

    AU - Franke, Lude

    AU - Geller, Frank

    AU - Geserick, Mandy

    AU - Hartikainen, Anna Liisa

    AU - Haworth, Claire M A

    AU - Hirschhorn, Joel N.

    AU - Hofman, Albert

    AU - Holm, Jens Christian

    AU - Horikoshi, Momoko

    AU - Hottenga, Jouke Jan

    AU - Huang, Jinyan

    AU - Kadarmideen, Haja N.

    AU - Kähönen, Mika

    AU - Kiess, Wieland

    AU - Lakka, Hanna Maaria

    AU - Lakka, Timo A.

    AU - Lewin, Alexandra M.

    AU - Liang, Liming

    AU - Lyytikäinen, Leo Pekka

    AU - Ma, Baoshan

    AU - Magnus, Per

    AU - McCormack, Shana E.

    AU - McMahon, George

    AU - Mentch, Frank D.

    AU - Middeldorp, Christel M.

    AU - Murray, Clare S.

    AU - Pahkala, Katja

    AU - Pers, Tune H.

    AU - Pfäffle, Roland

    AU - Postma, Dirkje S.

    AU - Power, Christine

    AU - Simpson, Angela

    AU - Sengpiel, Verena

    AU - Tiesler, Carla M T

    AU - Torrent, Maties

    AU - Uitterlinden, André G.

    AU - Van Meurs, Joyce B.

    AU - Vinding, Rebecca

    AU - Waage, Johannes

    AU - Wardle, Jane

    AU - Zeggini, Eleftheria

    AU - Zemel, Babette S.

    AU - Dedoussis, George V.

    AU - Pedersen, Oluf

    AU - Froguel, Philippe

    AU - Sunyer, Jordi

    AU - Plomin, Robert

    AU - Jacobsson, Bo

    AU - Hansen, Torben

    AU - Gonzalez, Juan R.

    AU - Custovic, Adnan

    AU - Raitakari, Olli T.

    AU - Pennell, Craig E.

    AU - Elisabeth Widén, Widén

    AU - Boomsma, Dorret I.

    AU - Koppelman, Gerard H.

    AU - Sebert, Sylvain

    AU - Järvelin, Marjo Riitta

    AU - Hyppönen, Elina

    AU - McCarthy, Mark I.

    AU - Lindi, Virpi

    AU - Harri, Niinikoski

    AU - Körner, Antje

    AU - Bønnelykke, Klaus

    AU - Heinrich, Joachim

    AU - Melbye, Mads

    AU - Rivadeneira, Fernando

    AU - Hakonarson, Hakon

    AU - Ring, Susan M.

    AU - Smith, George Davey

    AU - Sørensen, Thorkild I A

    AU - Timpson, Nicholas J.

    AU - Grant, Struan F A

    AU - Jaddoe, Vincent W V

    AU - Kalkwarf, Heidi J.

    AU - Lappe, Joan M.

    AU - Gilsanz, Vicente

    AU - Oberfield, Sharon E.

    AU - Shepherd, John A.

    AU - Kelly, Andrea

    PY - 2016/1/15

    Y1 - 2016/1/15

    N2 - A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown.We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores.We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value -8) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10-10) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.

    AB - A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown.We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores.We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value -8) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10-10) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.

    U2 - 10.1093/hmg/ddv472

    DO - 10.1093/hmg/ddv472

    M3 - Article

    VL - 25

    SP - 389

    EP - 403

    JO - Human Molecular Genetics

    JF - Human Molecular Genetics

    SN - 0964-6906

    IS - 2

    M1 - ddv472

    ER -