New loci associated with birth weight identify genetic links between intrauterine             growth and adult height and metabolism

Momoko Horikoshi; Hanieh Yaghootkar; Dennis O Mook-Kanamori; Ulla Sovio; H Rob Taal; Branwen J Hennig; Jonathan P Bradfield; Beate St Pourcain; David M Evans; Pimphen Charoen; Marika Kaakinen; Diana L Cousminer; Terho Lehtimäki; Eskil Kreiner-Møller; Nicole M Warrington; Mariona Bustamante; Bjarke Feenstra; Diane J Berry; Elisabeth Thiering; Thiemo Pfab; Sheila J Barton; Beverley M Shields; Marjan Kerkhof; Elisabeth M van Leeuwen; Anthony J Fulford; Zoltán Kutalik; Jing Hua Zhao; Marcel den Hoed; Anubha Mahajan; Virpi Lindi; Liang-Kee Goh; Jouke-Jan Hottenga; Ying Wu; Olli T Raitakari; Marie N Harder; Aline Meirhaeghe; Ioanna Ntalla; Rany M Salem; Karen A Jameson; Kaixin Zhou; Dorota M Monies; Vasiliki Lagou; Mirna Kirin; Jani Heikkinen; Linda S Adair; Fowzan S Alkuraya; Ali Al-Odaib; Philippe Amouyel; Ehm Astrid Andersson; Aaron Isaacs; Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC); Mark I. McCarthy; Vincent W. Jaddoe; Marjo-Riitta Jarvelin; Nicholas J Timpson; Inga Prokopenko; R. Freathy

doi:10.1038/ng.2477

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

Momoko Horikoshi
, Hanieh Yaghootkar
, Dennis O Mook-Kanamori
, Ulla Sovio
, H Rob Taal
, Branwen J Hennig
, Jonathan P Bradfield
, Beate St Pourcain
, David M Evans
, Pimphen Charoen
, Marika Kaakinen
, Diana L Cousminer
, Terho Lehtimäki
, Eskil Kreiner-Møller
, Nicole M Warrington
, Mariona Bustamante
, Bjarke Feenstra
, Diane J Berry
, Elisabeth Thiering
, Thiemo Pfab

Sheila J Barton, Beverley M Shields, Marjan Kerkhof, Elisabeth M van Leeuwen, Anthony J Fulford, Zoltán Kutalik, Jing Hua Zhao, Marcel den Hoed, Anubha Mahajan, Virpi Lindi, Liang-Kee Goh, Jouke-Jan Hottenga, Ying Wu, Olli T Raitakari, Marie N Harder, Aline Meirhaeghe, Ioanna Ntalla, Rany M Salem, Karen A Jameson, Kaixin Zhou, Dorota M Monies, Vasiliki Lagou, Mirna Kirin, Jani Heikkinen, Linda S Adair, Fowzan S Alkuraya, Ali Al-Odaib, Philippe Amouyel, Ehm Astrid Andersson, Aaron Isaacs, Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), Mark I. McCarthy^*, Vincent W. Jaddoe^*, Marjo-Riitta Jarvelin^*, Nicholas J Timpson^*, Inga Prokopenko^*, R. Freathy^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

Original language	English
Pages (from-to)	76-82
Number of pages	7
Journal	Nature Genetics
Volume	45
Issue number	1
DOIs	https://doi.org/10.1038/ng.2477
Publication status	Published - Jan 2013
Externally published	Yes

Keywords

Adult
Birth Weight/genetics
Blood Pressure/genetics
Body Height/genetics
Diabetes Mellitus, Type 2/genetics
Female
Fetal Development/genetics
Genetic Linkage
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Infant, Newborn
Male
Meta-Analysis as Topic
Polymorphism, Single Nucleotide
Quantitative Trait Loci

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10.1038/ng.2477Licence: Unspecified

https://www.research.ed.ac.uk/en/publications/af6ad460-4aa1-4e9f-9cb4-0920448e550aLicence: Other

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Horikoshi, M., Yaghootkar, H., Mook-Kanamori, D. O., Sovio, U., Taal, H. R., Hennig, B. J., Bradfield, J. P., St Pourcain, B., Evans, D. M., Charoen, P., Kaakinen, M., Cousminer, D. L., Lehtimäki, T., Kreiner-Møller, E., Warrington, N. M., Bustamante, M., Feenstra, B., Berry, D. J., Thiering, E., ... Freathy, R. (2013). New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism. Nature Genetics, 45(1), 76-82. https://doi.org/10.1038/ng.2477

@article{08965a11cc6547f2aab0c57c753b5e79,

title = "New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism",

abstract = "Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.",

keywords = "Adult, Birth Weight/genetics, Blood Pressure/genetics, Body Height/genetics, Diabetes Mellitus, Type 2/genetics, Female, Fetal Development/genetics, Genetic Linkage, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Infant, Newborn, Male, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Quantitative Trait Loci",

author = "Momoko Horikoshi and Hanieh Yaghootkar and Mook-Kanamori, \{Dennis O\} and Ulla Sovio and Taal, \{H Rob\} and Hennig, \{Branwen J\} and Bradfield, \{Jonathan P\} and \{St Pourcain\}, Beate and Evans, \{David M\} and Pimphen Charoen and Marika Kaakinen and Cousminer, \{Diana L\} and Terho Lehtim{\"a}ki and Eskil Kreiner-M{\o}ller and Warrington, \{Nicole M\} and Mariona Bustamante and Bjarke Feenstra and Berry, \{Diane J\} and Elisabeth Thiering and Thiemo Pfab and Barton, \{Sheila J\} and Shields, \{Beverley M\} and Marjan Kerkhof and \{van Leeuwen\}, \{Elisabeth M\} and Fulford, \{Anthony J\} and Zolt{\'a}n Kutalik and Zhao, \{Jing Hua\} and \{den Hoed\}, Marcel and Anubha Mahajan and Virpi Lindi and Liang-Kee Goh and Jouke-Jan Hottenga and Ying Wu and Raitakari, \{Olli T\} and Harder, \{Marie N\} and Aline Meirhaeghe and Ioanna Ntalla and Salem, \{Rany M\} and Jameson, \{Karen A\} and Kaixin Zhou and Monies, \{Dorota M\} and Vasiliki Lagou and Mirna Kirin and Jani Heikkinen and Adair, \{Linda S\} and Alkuraya, \{Fowzan S\} and Ali Al-Odaib and Philippe Amouyel and Andersson, \{Ehm Astrid\} and Aaron Isaacs and \{Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC)\} and McCarthy, \{Mark I.\} and Jaddoe, \{Vincent W.\} and Marjo-Riitta Jarvelin and Timpson, \{Nicholas J\} and Inga Prokopenko and R. Freathy",

year = "2013",

month = jan,

doi = "10.1038/ng.2477",

language = "English",

volume = "45",

pages = "76--82",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "1",

}

Horikoshi, M, Yaghootkar, H, Mook-Kanamori, DO, Sovio, U, Taal, HR, Hennig, BJ, Bradfield, JP, St Pourcain, B, Evans, DM, Charoen, P, Kaakinen, M, Cousminer, DL, Lehtimäki, T, Kreiner-Møller, E, Warrington, NM, Bustamante, M, Feenstra, B, Berry, DJ, Thiering, E, Pfab, T, Barton, SJ, Shields, BM, Kerkhof, M, van Leeuwen, EM, Fulford, AJ, Kutalik, Z, Zhao, JH, den Hoed, M, Mahajan, A, Lindi, V, Goh, L-K, Hottenga, J-J, Wu, Y, Raitakari, OT, Harder, MN, Meirhaeghe, A, Ntalla, I, Salem, RM, Jameson, KA, Zhou, K, Monies, DM, Lagou, V, Kirin, M, Heikkinen, J, Adair, LS, Alkuraya, FS, Al-Odaib, A, Amouyel, P, Andersson, EA, Isaacs, A, Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), McCarthy, MI, Jaddoe, VW, Jarvelin, M-R, Timpson, NJ, Prokopenko, I & Freathy, R 2013, 'New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism', Nature Genetics, vol. 45, no. 1, pp. 76-82. https://doi.org/10.1038/ng.2477

TY - JOUR

T1 - New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

AU - Horikoshi, Momoko

AU - Yaghootkar, Hanieh

AU - Mook-Kanamori, Dennis O

AU - Sovio, Ulla

AU - Taal, H Rob

AU - Hennig, Branwen J

AU - Bradfield, Jonathan P

AU - St Pourcain, Beate

AU - Evans, David M

AU - Charoen, Pimphen

AU - Kaakinen, Marika

AU - Cousminer, Diana L

AU - Lehtimäki, Terho

AU - Kreiner-Møller, Eskil

AU - Warrington, Nicole M

AU - Bustamante, Mariona

AU - Feenstra, Bjarke

AU - Berry, Diane J

AU - Thiering, Elisabeth

AU - Pfab, Thiemo

AU - Barton, Sheila J

AU - Shields, Beverley M

AU - Kerkhof, Marjan

AU - van Leeuwen, Elisabeth M

AU - Fulford, Anthony J

AU - Kutalik, Zoltán

AU - Zhao, Jing Hua

AU - den Hoed, Marcel

AU - Mahajan, Anubha

AU - Lindi, Virpi

AU - Goh, Liang-Kee

AU - Hottenga, Jouke-Jan

AU - Wu, Ying

AU - Raitakari, Olli T

AU - Harder, Marie N

AU - Meirhaeghe, Aline

AU - Ntalla, Ioanna

AU - Salem, Rany M

AU - Jameson, Karen A

AU - Zhou, Kaixin

AU - Monies, Dorota M

AU - Lagou, Vasiliki

AU - Kirin, Mirna

AU - Heikkinen, Jani

AU - Adair, Linda S

AU - Alkuraya, Fowzan S

AU - Al-Odaib, Ali

AU - Amouyel, Philippe

AU - Andersson, Ehm Astrid

AU - Isaacs, Aaron

AU - Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC)

AU - McCarthy, Mark I.

AU - Jaddoe, Vincent W.

AU - Jarvelin, Marjo-Riitta

AU - Timpson, Nicholas J

AU - Prokopenko, Inga

AU - Freathy, R.

PY - 2013/1

Y1 - 2013/1

N2 - Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

AB - Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

KW - Adult

KW - Birth Weight/genetics

KW - Blood Pressure/genetics

KW - Body Height/genetics

KW - Diabetes Mellitus, Type 2/genetics

KW - Female

KW - Fetal Development/genetics

KW - Genetic Linkage

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Infant, Newborn

KW - Male

KW - Meta-Analysis as Topic

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

U2 - 10.1038/ng.2477

DO - 10.1038/ng.2477

M3 - Article

C2 - 23202124

SN - 1061-4036

VL - 45

SP - 76

EP - 82

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

Abstract

Keywords

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