Novel Loci for Childhood Body Mass Index and Shared Heritability with Adult Cardiometabolic Traits

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged...

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Detalles Bibliográficos
Autores: Vogelezang, Suzanne, Bradfield, Jonathan P., Ahluwalia, Tarunveer S., Curtin, John A., Lakka, Timo A., Grarup, Niels, Scholz, Markus, Van der Most, Peter J., Monnereau, Claire, Stergiakouli, Evie, Heiskala, Anni, Horikoshi, Momoko, Fedko, Iryna O., Vilor Tejedor, Natalia, Cousminer, Diana L., Standl, Marie, Wang, Carol A., Viikari, Jorma, Geller, Frank, Iñiguez, Carmen, Pitkanen, Niina, Chesi, Alessandra, Bacelis, Jonas, Yengo, Loic, Torrent, Maties, Ntalla, Ioanna, Helgeland, Oyvind, Selzam, Saskia, Vonk, Judith M., Zafarmand, Mohammed H., Heude, Barbara, Farooqi, Ismaa Sadaf, Alyass, Akram, Beaumont, Robin N., Have, Christian T., Rzehak, Peter, Bilbao Catalá, José Ramón, Schnurr, Theresia M., Barroso, Ines, Bonnelykke, Klaus, Beilin, Lawrence J., Carstensen, Lisbeth, Charles, Marie Aline, Chawes, Bo, Clement, Karine, Closa Monasterolo, Ricardo, Custovic, Adnan, Eriksson, Johan G., Escribano, Joaquín, Groen-Blokhuis, Maria, Grote, Veit, Gruszfeld, Dariusz, Hakonarson, Hakon, Hansen, Torben, Hattersley, Andrew T., Hollensted, Mette, Hottenga, Jouke Jan, Hypponen, Elina, Johansson, Stefan, Joro, Raimo, Kahonen, Mika, Karhunen, Ville, Kiess, Wieland, Knight, Bridget A., Koletzko, Berthold, Kuehnapfel, Andreas, Landgraf, Kathrin, Langhendries, Jean-Paul, Lehtimaki, Terho, Leinonen, Jaakko T., Li, Aihuali, Lindi, Virpi, Lowry, Estelle, Bustamante, Mariona, Medina Gómez, Carolina, Melbye, Mads, Michaelsen, Kim F., Morgen, Camilla S., Mori, Trevor A., Nielsen, Tenna R. H., Niinikoski, Harri, Oldehinkel, Albertine J., Pahkala, Katja, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E., Power, Christine, Reijneveld, Sijmen A., Rivadeneira, Fernando, Simpson, Angela, Sly, Peter D., Stokholm, Jakob, Teo, Kook K., Thiering, Elisabeth, Timpson, Nicholas J., Uitterlinden, Andre G., Van Beijsterveldt, Catharina E. M., Van Schaik, Barbera D. C., Vaudel, Marc, Verduci, Elvira, Vinding, Rebecca K., Vogel, Mandy, Zeggini, Eleftheria, Sebert, Sylvain, Lind, Mads V., Brown, Christopher D., Santa Marina, Loreto, Reischl, Eva, Frithioff-Bojsoe, Christine, Meyre, David, Wheeler, Eleanor, Ong, Ken, Nohr, Ellen A., Vrijkotte, Tanja G. M., Koppelman, Gerard H., Plomin, Robert, Njolstad, Pal R., Dedoussis, George D., Froguel, Philippe, Sorensen, Thorkild I. A., Jacobsson, Bo, Freathy, Rachel M., Zemel, Babette S., Raitakari, Olli, Vrijheid, Martine, Feenstra, Bjarke, Lyytikainen, Leo-Pekka, Snieder, Harold, Kirsten, Holger, Holt, Patrick G., Heinrich, Joachim, Widen, Elisabeth, Sunyer, Jordi, Boomsma, Dorret I., Jarvelin, Marjo-Riitta, Koerner, Antje, Smith, George Davey, Holm, Jens-Christian, Atalay, Mustafa, Murray, Clare, Bisgaard, Hans, McCarthy, Mark I., Jaddoe, Vincent W. V., Grant, Struan F. A., Felix, Janine F.
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/50191
Acceso en línea:http://hdl.handle.net/10810/50191
Access Level:acceso abierto
Palabra clave:prostate-specific antigen
genome-wide association
mendelian randomization
cardiovascular risk
genetic-variation
pooled analysis
young-adults
obesity
overweight
adiposity
id ES_8804e6cc3d787da885aaf8cede46d85d
oai_identifier_str oai:addi.ehu.eus:10810/50191
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Novel Loci for Childhood Body Mass Index and Shared Heritability with Adult Cardiometabolic Traits
title Novel Loci for Childhood Body Mass Index and Shared Heritability with Adult Cardiometabolic Traits
spellingShingle Novel Loci for Childhood Body Mass Index and Shared Heritability with Adult Cardiometabolic Traits
Vogelezang, Suzanne
prostate-specific antigen
genome-wide association
mendelian randomization
cardiovascular risk
genetic-variation
pooled analysis
young-adults
obesity
overweight
adiposity
title_short Novel Loci for Childhood Body Mass Index and Shared Heritability with Adult Cardiometabolic Traits
title_full Novel Loci for Childhood Body Mass Index and Shared Heritability with Adult Cardiometabolic Traits
title_fullStr Novel Loci for Childhood Body Mass Index and Shared Heritability with Adult Cardiometabolic Traits
title_full_unstemmed Novel Loci for Childhood Body Mass Index and Shared Heritability with Adult Cardiometabolic Traits
title_sort Novel Loci for Childhood Body Mass Index and Shared Heritability with Adult Cardiometabolic Traits
dc.creator.none.fl_str_mv Vogelezang, Suzanne
Bradfield, Jonathan P.
Ahluwalia, Tarunveer S.
Curtin, John A.
Lakka, Timo A.
Grarup, Niels
Scholz, Markus
Van der Most, Peter J.
Monnereau, Claire
Stergiakouli, Evie
Heiskala, Anni
Horikoshi, Momoko
Fedko, Iryna O.
Vilor Tejedor, Natalia
Cousminer, Diana L.
Standl, Marie
Wang, Carol A.
Viikari, Jorma
Geller, Frank
Iñiguez, Carmen
Pitkanen, Niina
Chesi, Alessandra
Bacelis, Jonas
Yengo, Loic
Torrent, Maties
Ntalla, Ioanna
Helgeland, Oyvind
Selzam, Saskia
Vonk, Judith M.
Zafarmand, Mohammed H.
Heude, Barbara
Farooqi, Ismaa Sadaf
Alyass, Akram
Beaumont, Robin N.
Have, Christian T.
Rzehak, Peter
Bilbao Catalá, José Ramón
Schnurr, Theresia M.
Barroso, Ines
Bonnelykke, Klaus
Beilin, Lawrence J.
Carstensen, Lisbeth
Charles, Marie Aline
Chawes, Bo
Clement, Karine
Closa Monasterolo, Ricardo
Custovic, Adnan
Eriksson, Johan G.
Escribano, Joaquín
Groen-Blokhuis, Maria
Grote, Veit
Gruszfeld, Dariusz
Hakonarson, Hakon
Hansen, Torben
Hattersley, Andrew T.
Hollensted, Mette
Hottenga, Jouke Jan
Hypponen, Elina
Johansson, Stefan
Joro, Raimo
Kahonen, Mika
Karhunen, Ville
Kiess, Wieland
Knight, Bridget A.
Koletzko, Berthold
Kuehnapfel, Andreas
Landgraf, Kathrin
Langhendries, Jean-Paul
Lehtimaki, Terho
Leinonen, Jaakko T.
Li, Aihuali
Lindi, Virpi
Lowry, Estelle
Bustamante, Mariona
Medina Gómez, Carolina
Melbye, Mads
Michaelsen, Kim F.
Morgen, Camilla S.
Mori, Trevor A.
Nielsen, Tenna R. H.
Niinikoski, Harri
Oldehinkel, Albertine J.
Pahkala, Katja
Panoutsopoulou, Kalliope
Pedersen, Oluf
Pennell, Craig E.
Power, Christine
Reijneveld, Sijmen A.
Rivadeneira, Fernando
Simpson, Angela
Sly, Peter D.
Stokholm, Jakob
Teo, Kook K.
Thiering, Elisabeth
Timpson, Nicholas J.
Uitterlinden, Andre G.
Van Beijsterveldt, Catharina E. M.
Van Schaik, Barbera D. C.
Vaudel, Marc
Verduci, Elvira
Vinding, Rebecca K.
Vogel, Mandy
Zeggini, Eleftheria
Sebert, Sylvain
Lind, Mads V.
Brown, Christopher D.
Santa Marina, Loreto
Reischl, Eva
Frithioff-Bojsoe, Christine
Meyre, David
Wheeler, Eleanor
Ong, Ken
Nohr, Ellen A.
Vrijkotte, Tanja G. M.
Koppelman, Gerard H.
Plomin, Robert
Njolstad, Pal R.
Dedoussis, George D.
Froguel, Philippe
Sorensen, Thorkild I. A.
Jacobsson, Bo
Freathy, Rachel M.
Zemel, Babette S.
Raitakari, Olli
Vrijheid, Martine
Feenstra, Bjarke
Lyytikainen, Leo-Pekka
Snieder, Harold
Kirsten, Holger
Holt, Patrick G.
Heinrich, Joachim
Widen, Elisabeth
Sunyer, Jordi
Boomsma, Dorret I.
Jarvelin, Marjo-Riitta
Koerner, Antje
Smith, George Davey
Holm, Jens-Christian
Atalay, Mustafa
Murray, Clare
Bisgaard, Hans
McCarthy, Mark I.
Jaddoe, Vincent W. V.
Grant, Struan F. A.
Felix, Janine F.
author Vogelezang, Suzanne
author_facet Vogelezang, Suzanne
Bradfield, Jonathan P.
Ahluwalia, Tarunveer S.
Curtin, John A.
Lakka, Timo A.
Grarup, Niels
Scholz, Markus
Van der Most, Peter J.
Monnereau, Claire
Stergiakouli, Evie
Heiskala, Anni
Horikoshi, Momoko
Fedko, Iryna O.
Vilor Tejedor, Natalia
Cousminer, Diana L.
Standl, Marie
Wang, Carol A.
Viikari, Jorma
Geller, Frank
Iñiguez, Carmen
Pitkanen, Niina
Chesi, Alessandra
Bacelis, Jonas
Yengo, Loic
Torrent, Maties
Ntalla, Ioanna
Helgeland, Oyvind
Selzam, Saskia
Vonk, Judith M.
Zafarmand, Mohammed H.
Heude, Barbara
Farooqi, Ismaa Sadaf
Alyass, Akram
Beaumont, Robin N.
Have, Christian T.
Rzehak, Peter
Bilbao Catalá, José Ramón
Schnurr, Theresia M.
Barroso, Ines
Bonnelykke, Klaus
Beilin, Lawrence J.
Carstensen, Lisbeth
Charles, Marie Aline
Chawes, Bo
Clement, Karine
Closa Monasterolo, Ricardo
Custovic, Adnan
Eriksson, Johan G.
Escribano, Joaquín
Groen-Blokhuis, Maria
Grote, Veit
Gruszfeld, Dariusz
Hakonarson, Hakon
Hansen, Torben
Hattersley, Andrew T.
Hollensted, Mette
Hottenga, Jouke Jan
Hypponen, Elina
Johansson, Stefan
Joro, Raimo
Kahonen, Mika
Karhunen, Ville
Kiess, Wieland
Knight, Bridget A.
Koletzko, Berthold
Kuehnapfel, Andreas
Landgraf, Kathrin
Langhendries, Jean-Paul
Lehtimaki, Terho
Leinonen, Jaakko T.
Li, Aihuali
Lindi, Virpi
Lowry, Estelle
Bustamante, Mariona
Medina Gómez, Carolina
Melbye, Mads
Michaelsen, Kim F.
Morgen, Camilla S.
Mori, Trevor A.
Nielsen, Tenna R. H.
Niinikoski, Harri
Oldehinkel, Albertine J.
Pahkala, Katja
Panoutsopoulou, Kalliope
Pedersen, Oluf
Pennell, Craig E.
Power, Christine
Reijneveld, Sijmen A.
Rivadeneira, Fernando
Simpson, Angela
Sly, Peter D.
Stokholm, Jakob
Teo, Kook K.
Thiering, Elisabeth
Timpson, Nicholas J.
Uitterlinden, Andre G.
Van Beijsterveldt, Catharina E. M.
Van Schaik, Barbera D. C.
Vaudel, Marc
Verduci, Elvira
Vinding, Rebecca K.
Vogel, Mandy
Zeggini, Eleftheria
Sebert, Sylvain
Lind, Mads V.
Brown, Christopher D.
Santa Marina, Loreto
Reischl, Eva
Frithioff-Bojsoe, Christine
Meyre, David
Wheeler, Eleanor
Ong, Ken
Nohr, Ellen A.
Vrijkotte, Tanja G. M.
Koppelman, Gerard H.
Plomin, Robert
Njolstad, Pal R.
Dedoussis, George D.
Froguel, Philippe
Sorensen, Thorkild I. A.
Jacobsson, Bo
Freathy, Rachel M.
Zemel, Babette S.
Raitakari, Olli
Vrijheid, Martine
Feenstra, Bjarke
Lyytikainen, Leo-Pekka
Snieder, Harold
Kirsten, Holger
Holt, Patrick G.
Heinrich, Joachim
Widen, Elisabeth
Sunyer, Jordi
Boomsma, Dorret I.
Jarvelin, Marjo-Riitta
Koerner, Antje
Smith, George Davey
Holm, Jens-Christian
Atalay, Mustafa
Murray, Clare
Bisgaard, Hans
McCarthy, Mark I.
Jaddoe, Vincent W. V.
Grant, Struan F. A.
Felix, Janine F.
author_role author
author2 Bradfield, Jonathan P.
Ahluwalia, Tarunveer S.
Curtin, John A.
Lakka, Timo A.
Grarup, Niels
Scholz, Markus
Van der Most, Peter J.
Monnereau, Claire
Stergiakouli, Evie
Heiskala, Anni
Horikoshi, Momoko
Fedko, Iryna O.
Vilor Tejedor, Natalia
Cousminer, Diana L.
Standl, Marie
Wang, Carol A.
Viikari, Jorma
Geller, Frank
Iñiguez, Carmen
Pitkanen, Niina
Chesi, Alessandra
Bacelis, Jonas
Yengo, Loic
Torrent, Maties
Ntalla, Ioanna
Helgeland, Oyvind
Selzam, Saskia
Vonk, Judith M.
Zafarmand, Mohammed H.
Heude, Barbara
Farooqi, Ismaa Sadaf
Alyass, Akram
Beaumont, Robin N.
Have, Christian T.
Rzehak, Peter
Bilbao Catalá, José Ramón
Schnurr, Theresia M.
Barroso, Ines
Bonnelykke, Klaus
Beilin, Lawrence J.
Carstensen, Lisbeth
Charles, Marie Aline
Chawes, Bo
Clement, Karine
Closa Monasterolo, Ricardo
Custovic, Adnan
Eriksson, Johan G.
Escribano, Joaquín
Groen-Blokhuis, Maria
Grote, Veit
Gruszfeld, Dariusz
Hakonarson, Hakon
Hansen, Torben
Hattersley, Andrew T.
Hollensted, Mette
Hottenga, Jouke Jan
Hypponen, Elina
Johansson, Stefan
Joro, Raimo
Kahonen, Mika
Karhunen, Ville
Kiess, Wieland
Knight, Bridget A.
Koletzko, Berthold
Kuehnapfel, Andreas
Landgraf, Kathrin
Langhendries, Jean-Paul
Lehtimaki, Terho
Leinonen, Jaakko T.
Li, Aihuali
Lindi, Virpi
Lowry, Estelle
Bustamante, Mariona
Medina Gómez, Carolina
Melbye, Mads
Michaelsen, Kim F.
Morgen, Camilla S.
Mori, Trevor A.
Nielsen, Tenna R. H.
Niinikoski, Harri
Oldehinkel, Albertine J.
Pahkala, Katja
Panoutsopoulou, Kalliope
Pedersen, Oluf
Pennell, Craig E.
Power, Christine
Reijneveld, Sijmen A.
Rivadeneira, Fernando
Simpson, Angela
Sly, Peter D.
Stokholm, Jakob
Teo, Kook K.
Thiering, Elisabeth
Timpson, Nicholas J.
Uitterlinden, Andre G.
Van Beijsterveldt, Catharina E. M.
Van Schaik, Barbera D. C.
Vaudel, Marc
Verduci, Elvira
Vinding, Rebecca K.
Vogel, Mandy
Zeggini, Eleftheria
Sebert, Sylvain
Lind, Mads V.
Brown, Christopher D.
Santa Marina, Loreto
Reischl, Eva
Frithioff-Bojsoe, Christine
Meyre, David
Wheeler, Eleanor
Ong, Ken
Nohr, Ellen A.
Vrijkotte, Tanja G. M.
Koppelman, Gerard H.
Plomin, Robert
Njolstad, Pal R.
Dedoussis, George D.
Froguel, Philippe
Sorensen, Thorkild I. A.
Jacobsson, Bo
Freathy, Rachel M.
Zemel, Babette S.
Raitakari, Olli
Vrijheid, Martine
Feenstra, Bjarke
Lyytikainen, Leo-Pekka
Snieder, Harold
Kirsten, Holger
Holt, Patrick G.
Heinrich, Joachim
Widen, Elisabeth
Sunyer, Jordi
Boomsma, Dorret I.
Jarvelin, Marjo-Riitta
Koerner, Antje
Smith, George Davey
Holm, Jens-Christian
Atalay, Mustafa
Murray, Clare
Bisgaard, Hans
McCarthy, Mark I.
Jaddoe, Vincent W. V.
Grant, Struan F. A.
Felix, Janine F.
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dc.contributor.none.fl_str_mv European Commission
dc.subject.none.fl_str_mv prostate-specific antigen
genome-wide association
mendelian randomization
cardiovascular risk
genetic-variation
pooled analysis
young-adults
obesity
overweight
adiposity
topic prostate-specific antigen
genome-wide association
mendelian randomization
cardiovascular risk
genetic-variation
pooled analysis
young-adults
obesity
overweight
adiposity
description The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood. Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/50191
url http://hdl.handle.net/10810/50191
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/EC/FP7/322605
info:eu-repo/grantAgreement/EC/H2020/648916
info:eu-repo/grantAgreement/EC/FP7/279153
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008718
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869412519850803200
spelling Novel Loci for Childhood Body Mass Index and Shared Heritability with Adult Cardiometabolic TraitsVogelezang, SuzanneBradfield, Jonathan P.Ahluwalia, Tarunveer S.Curtin, John A.Lakka, Timo A.Grarup, NielsScholz, MarkusVan der Most, Peter J.Monnereau, ClaireStergiakouli, EvieHeiskala, AnniHorikoshi, MomokoFedko, Iryna O.Vilor Tejedor, NataliaCousminer, Diana L.Standl, MarieWang, Carol A.Viikari, JormaGeller, FrankIñiguez, CarmenPitkanen, NiinaChesi, AlessandraBacelis, JonasYengo, LoicTorrent, MatiesNtalla, IoannaHelgeland, OyvindSelzam, SaskiaVonk, Judith M.Zafarmand, Mohammed H.Heude, BarbaraFarooqi, Ismaa SadafAlyass, AkramBeaumont, Robin N.Have, Christian T.Rzehak, PeterBilbao Catalá, José RamónSchnurr, Theresia M.Barroso, InesBonnelykke, KlausBeilin, Lawrence J.Carstensen, LisbethCharles, Marie AlineChawes, BoClement, KarineClosa Monasterolo, RicardoCustovic, AdnanEriksson, Johan G.Escribano, JoaquínGroen-Blokhuis, MariaGrote, VeitGruszfeld, DariuszHakonarson, HakonHansen, TorbenHattersley, Andrew T.Hollensted, MetteHottenga, Jouke JanHypponen, ElinaJohansson, StefanJoro, RaimoKahonen, MikaKarhunen, VilleKiess, WielandKnight, Bridget A.Koletzko, BertholdKuehnapfel, AndreasLandgraf, KathrinLanghendries, Jean-PaulLehtimaki, TerhoLeinonen, Jaakko T.Li, AihualiLindi, VirpiLowry, EstelleBustamante, MarionaMedina Gómez, CarolinaMelbye, MadsMichaelsen, Kim F.Morgen, Camilla S.Mori, Trevor A.Nielsen, Tenna R. H.Niinikoski, HarriOldehinkel, Albertine J.Pahkala, KatjaPanoutsopoulou, KalliopePedersen, OlufPennell, Craig E.Power, ChristineReijneveld, Sijmen A.Rivadeneira, FernandoSimpson, AngelaSly, Peter D.Stokholm, JakobTeo, Kook K.Thiering, ElisabethTimpson, Nicholas J.Uitterlinden, Andre G.Van Beijsterveldt, Catharina E. M.Van Schaik, Barbera D. C.Vaudel, MarcVerduci, ElviraVinding, Rebecca K.Vogel, MandyZeggini, EleftheriaSebert, SylvainLind, Mads V.Brown, Christopher D.Santa Marina, LoretoReischl, EvaFrithioff-Bojsoe, ChristineMeyre, DavidWheeler, EleanorOng, KenNohr, Ellen A.Vrijkotte, Tanja G. M.Koppelman, Gerard H.Plomin, RobertNjolstad, Pal R.Dedoussis, George D.Froguel, PhilippeSorensen, Thorkild I. A.Jacobsson, BoFreathy, Rachel M.Zemel, Babette S.Raitakari, OlliVrijheid, MartineFeenstra, BjarkeLyytikainen, Leo-PekkaSnieder, HaroldKirsten, HolgerHolt, Patrick G.Heinrich, JoachimWiden, ElisabethSunyer, JordiBoomsma, Dorret I.Jarvelin, Marjo-RiittaKoerner, AntjeSmith, George DaveyHolm, Jens-ChristianAtalay, MustafaMurray, ClareBisgaard, HansMcCarthy, Mark I.Jaddoe, Vincent W. V.Grant, Struan F. A.Felix, Janine F.prostate-specific antigengenome-wide associationmendelian randomizationcardiovascular riskgenetic-variationpooled analysisyoung-adultsobesityoverweightadiposityThe genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood. Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI.CP received funding from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. MMcC is a Wellcome Senior Investigator and an NIHR Senior Investigator. MMcC received funding from Wellcome (090532, 106130, 098381, 203141, 212259), NIDDK (U01DK105535), and NIHR (NF-SI-0617-10090). TGMV was supported by ZonMW (TOP 40-00812-9811010). DLC was supported by the American Diabetes Association Grant 1-17-PDF-077. SFAG is supported by the Daniel B. Burke Chair for Diabetes Research and NIH Grant R01 HD058886. NVT is funded by a pre-doctoral grant from the Agencia de Gestio d'Ajuts Universitaris i de Recerca (2017 FI_B 00636), Generalitat de Catalunya -Fons Social Europeu. BK received personal funding from the European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG -no. 322605). BF was supported by an Oak Foundation Fellowship. RMF and RNB are supported by Sir Henry Dale Fellowship (Wellcome Trust and Royal Society grant: WT104150). ATH is supported by a Wellcome Trust Senior Investigator award (grant number 098395/Z/12/Z). DM is supported by a Canada Research Chair. DLC was supported by the American Diabetes Association Grant 1-17-PDF077. JTL was supported by the Finnish Cultural Foundation. DIB received a KNAW Academy Professor Award (PAH/6635). MH received PhD scholarship funding from TARGET (http://target.ku.dk), The Danish Diabetes Academy (http://danishdiabetesacademy.dk) and the Copenhagen Graduate School of Health and Medical Sciences. VWVJ received funding from the Netherlands Organization for Health Research and Development (VIDI 016.136.361) and the European Research Council (ERC-2014-CoG-648916). ISF was supported by the European Research Council, Wellcome Trust (098497/Z/12/Z), Medical Research Council (MRC_MC_UU_12012/5), the NIHR Cambridge Biomedical Research Centre, the Botnar Foundation, the Bernard Wolfe Health Neuroscience Endowment and the European Community's Seventh Framework Programme (FP7/2007-2013) project Beta-JUDO n degrees 279153. IB acknowledges funding from Wellcome (WT206194). ES works in a unit that receives funding from the University of Bristol and the UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_00011/1). KC received funds from the French National Agency of Research, F-CRIN/FORCE. All funding for the studies that provided the underlying data for this manuscript can be found in S1 Text. The funders had no role in study design, data collection and analysis, data interpretation, decision to publish, or preparation of the manuscript. EditorialPublic Library ScienceEuropean Commission202120212020info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/50191reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/EC/FP7/322605info:eu-repo/grantAgreement/EC/H2020/648916info:eu-repo/grantAgreement/EC/FP7/279153https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008718info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0)Atribución 3.0 Españaoai:addi.ehu.eus:10810/501912026-06-18T09:23:17Z
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