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; Torben Hansen; Torben Jørgensen; Tuomas O Kilpeläinen; Louise Pedersen; Allan Vaag; Nadja Hawwa Vissing; Daniel R Witte; Oluf Pedersen; Klaus Bønnelykke; Hans Bisgaard; Meta-Analyses of Glucose- and Insulin-related traits Consortium (MAGIC)

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 PfabSheila 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, Torben Hansen, Torben Jørgensen, Tuomas O Kilpeläinen, Louise Pedersen, Allan Vaag, Nadja Hawwa Vissing, Daniel R Witte, Oluf Pedersen, Klaus Bønnelykke, Hans Bisgaard, Meta-Analyses of Glucose- and Insulin-related traits Consortium (MAGIC)

194 Citations (Scopus)

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
Journal	Nature Genetics
Volume	45
Issue number	1
Pages (from-to)	76-82
Number of pages	7
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.2477
Publication status	Published - Jan 2013

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.2477

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

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, Hansen, T, Jørgensen, T, Kilpeläinen, TO, Pedersen, L, Vaag, A, Vissing, NH, Witte, DR, Pedersen, O , Bønnelykke, K, Bisgaard, H & Meta-Analyses of Glucose- and Insulin-related traits Consortium (MAGIC) 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

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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, Blood Pressure, Body Height, Diabetes Mellitus, Type 2, Female, Fetal Development, 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 Torben Hansen and Torben J{\o}rgensen and Kilpel{\"a}inen, {Tuomas O} and Louise Pedersen and Allan Vaag and Vissing, {Nadja Hawwa} and Witte, {Daniel R} and Oluf Pedersen and Klaus B{\o}nnelykke and Hans Bisgaard and {Meta-Analyses of Glucose- and Insulin-related traits Consortium (MAGIC)}",

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doi = "10.1038/ng.2477",

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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 - Hansen, Torben

AU - Jørgensen, Torben

AU - Kilpeläinen, Tuomas O

AU - Pedersen, Louise

AU - Vaag, Allan

AU - Vissing, Nadja Hawwa

AU - Witte, Daniel R

AU - Pedersen, Oluf

AU - Bønnelykke, Klaus

AU - Bisgaard, Hans

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

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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.

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KW - Blood Pressure

KW - Body Height

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Fetal Development

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

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SN - 1061-4036

VL - 45

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EP - 82

JO - Nature: New biology

JF - Nature: New biology

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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