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; Niina Pitkänen; Raimo Joro; Alana Cavadino; Ville Huikari; Steve Franks; Maria M Groen-Blokhuis; Diana L Cousminer; Julie A Marsh; Terho Lehtimäki; John A Curtin; Jesus Vioque; Tarun Veer Singh Ahluwalia; Ronny Myhre; Thomas S Price; 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; Jens-Christian Holm; Haja N Kadarmideen; Tune H. Pers; Oluf Pedersen; Torben Hansen; Mads Melbye; Thorkild I A Sørensen; Bone Mineral Density in Childhood Study (BMDCS) Consortium

doi:10.1093/hmg/ddv472

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, Niina Pitkänen, Raimo Joro, Alana Cavadino, Ville Huikari, Steve Franks, Maria M Groen-Blokhuis, Diana L Cousminer, Julie A Marsh, Terho LehtimäkiJohn A Curtin, Jesus Vioque, Tarun Veer Singh Ahluwalia, Ronny Myhre, Thomas S Price, 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, Jens-Christian Holm, Haja N Kadarmideen, Tune H. Pers, Oluf Pedersen, Torben Hansen, Mads Melbye, Thorkild I A Sørensen, Bone Mineral Density in Childhood Study (BMDCS) Consortium

158 Citationer (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 < 5 × 10^-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.

Originalsprog	Engelsk
Tidsskrift	Human Molecular Genetics
Vol/bind	25
Udgave nummer	2
Sider (fra-til)	389-403
ISSN	0964-6906
DOI	https://doi.org/10.1093/hmg/ddv472
Status	Udgivet - 15 jan. 2016

FN’s Verdensmål

Dette resultat bidrager til følgende verdensmål

Adgang til dokumentet

10.1093/hmg/ddv472

ddv472.pdfForlagets udgivne version, 449 KB

Citationsformater

Felix, J. F., Bradfield, J. P., Monnereau, C., van der Valk, R. J. P., Stergiakouli, E., Chesi, A., Gaillard, R., Feenstra, B., Thiering, E., Kreiner-Møller, E., Mahajan, A., Pitkänen, N., Joro, R., Cavadino, A., Huikari, V., Franks, S., Groen-Blokhuis, M. M., Cousminer, D. L., Marsh, J. A., ... Bone Mineral Density in Childhood Study (BMDCS) Consortium (2016). Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. Human Molecular Genetics, 25(2), 389-403. https://doi.org/10.1093/hmg/ddv472

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, Pitkänen, N, Joro, R, Cavadino, A, Huikari, V, Franks, S, Groen-Blokhuis, MM, Cousminer, DL, Marsh, JA, Lehtimäki, T, Curtin, JA, Vioque, J, Ahluwalia, TVS, Myhre, R, Price, TS, Vilor-Tejedor, N, 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, A-L, Haworth, CMA, Hirschhorn, JN, Holm, J-C , Kadarmideen, HN , Pers, TH , Pedersen, O , Hansen, T , Melbye, M , Sørensen, TIA & Bone Mineral Density in Childhood Study (BMDCS) Consortium 2016, 'Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index', Human Molecular Genetics, bind 25, nr. 2, s. 389-403. https://doi.org/10.1093/hmg/ddv472

@article{47aafe9e027941a2bfa71dd0e8afef8a,

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 < 5 × 10-8) 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 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, {Tarun Veer Singh} and Ronny Myhre and Price, {Thomas S} and Natalia 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 Anna-Liisa Hartikainen and Haworth, {Claire M A} and Hirschhorn, {Joel N} and Jens-Christian Holm and Kadarmideen, {Haja N} and Pers, {Tune H.} and Oluf Pedersen and Torben Hansen and Mads Melbye and S{\o}rensen, {Thorkild I A} and {Bone Mineral Density in Childhood Study (BMDCS) Consortium}",

year = "2016",

month = jan,

day = "15",

doi = "10.1093/hmg/ddv472",

language = "English",

volume = "25",

pages = "389--403",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "2",

}

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 - Pitkänen, Niina

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, Tarun Veer Singh

AU - Myhre, Ronny

AU - Price, Thomas S

AU - Vilor-Tejedor, Natalia

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 - Holm, Jens-Christian

AU - Kadarmideen, Haja N

AU - Pers, Tune H.

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Melbye, Mads

AU - Sørensen, Thorkild I A

AU - Bone Mineral Density in Childhood Study (BMDCS) Consortium

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 < 5 × 10-8) 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 < 5 × 10-8) 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 - Journal article

C2 - 26604143

SN - 0964-6906

VL - 25

SP - 389

EP - 403

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 2

ER -

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

Abstract

FN’s Verdensmål

Adgang til dokumentet

Fingeraftryk

Citationsformater