Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

被引：128

作者：

Vogelezang, Suzanne ^{[1
,2
,3
]}

Bradfield, Jonathan P. ^{[4
,5
]}

Ahluwalia, Tarunveer S. ^{[6
,7
,8
]}

Curtin, John A. ^{[9
,10
]}

Lakka, Timo A. ^{[11
,12
,13
]}

Grarup, Niels ^{[8
]}

Scholz, Markus ^{[14
,15
]}

van der Most, Peter J. ^{[16
]}

Monnereau, Claire ^{[1
,2
,3
]}

Stergiakouli, Evie ^{[17
,18
,19
]}

Heiskala, Anni ^{[20
]}

Horikoshi, Momoko ^{[21
,22
,23
]}

Fedko, Iryna O. ^{[24
]}

Vilor-Tejedor, Natalia ^{[25
,26
,27
,28
]}

Cousminer, Diana L. ^{[29
,30
]}

Standl, Marie ^{[31
]}

Wang, Carol A. ^{[32
]}

Viikari, Jorma ^{[33
,34
]}

Geller, Frank ^{[35
]}

iniguez, Carmen ^{[28
,36
,37
]}

Pitkanen, Niina ^{[38
,39
,40
]}

Chesi, Alessandra ^{[29
]}

Bacelis, Jonas ^{[41
,42
]}

Yengo, Loic ^{[43
,44
]}

Torrent, Maties ^{[45
,46
]}

Ntalla, Ioanna ^{[47
]}

Helgeland, Oyvind ^{[48
,49
]}

Selzam, Saskia ^{[50
]}

Vonk, Judith M. ^{[51
]}

Zafarmand, Mohammed H. ^{[52
,53
,54
]}

Heude, Barbara ^{[55
]}

Farooqi, Ismaa Sadaf ^{[56
,57
]}

Alyass, Akram ^{[58
]}

Beaumont, Robin N. ^{[59
]}

Have, Christian T. ^{[8
]}

Rzehak, Peter ^{[60
]}

Bilbao, Jose Ramon ^{[61
,62
,63
]}

Schnurr, Theresia M. ^{[8
]}

Barroso, Ines ^{[64
,65
]}

Bonnelykke, Klaus ^{[6
]}

Beilin, Lawrence J. ^{[66
]}

Carstensen, Lisbeth ^{[35
]}

Charles, Marie-Aline ^{[55
]}

Chawes, Bo ^{[6
]}

Clement, Karine ^{[67
]}

Closa-Monasterolo, Ricardo ^{[68
]}

Custovic, Adnan ^{[69
]}

Eriksson, Johan G. ^{[70
,71
,72
]}

Escribano, Joaquin ^{[68
]}

Groen-Blokhuis, Maria ^{[24
]}

机构：

[1] Erasmus MC, Univ Med Ctr, Generat R Study Grp, Rotterdam, Netherlands

[2] Erasmus MC, Univ Med Ctr, Dept Pediat, Rotterdam, Netherlands

[3] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[4] Quantinuum Res LLC, San Diego, CA USA

[5] Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Genom, Philadelphia, PA 19104 USA

[6] Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark

[7] Steno Diabet Ctr Copenhagen, Gentofte, Denmark

[8] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark

[9] Univ Manchester, Div Infect Immun & Resp Med, Sch Biol Sci, Manchester Acad,Hlth Sci Ctr, Manchester, Lancs, England

[10] Manchester Univ NHS Fdn Trust, Manchester, Lancs, England

[11] Univ Eastern Finland, Inst Biomed, Physiol, Kuopio, Finland

[12] Fdn Res Hlth Exercise & Nutr, Kuopio Res Inst Exercise Med, Kuopio, Finland

[13] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland

[14] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany

[15] Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany

[16] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands

[17] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England

[18] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England

[19] Univ Bristol, Sch Oral & Dent Sci, Bristol, Avon, England

[20] Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland

[21] Univ Oxford, Wellcome Ctr Human Genet, Oxford, England

[22] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England

[23] RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[24] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[25] ISGlobal, Barcelona, Spain

[26] Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Spain

[27] Pasqual Maragall Fdn, BarcelonaBeta Brain Res Ctr BBRC, Barcelona, Spain

[28] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain

[29] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA

[30] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA

[31] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany

[32] Univ Newcastle, Sch Med & Publ Hlth, Fac Med & Hlth, Newcastle, NSW, Australia

[33] Univ Turku, Dept Med, Turku, Finland

[34] Turku Univ Hosp, Div Med, Turku, Finland

[35] Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark

[36] Univ Valencia, Dept Stat & Computat Res, Valencia, Spain

[37] FISABIO Univ Jaume I Univ Valencia, Epidemiol & Environm Hlth Joint Res Unit, Valencia, Spain

[38] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland

[39] Univ Turku, Ctr Populat Hlth Res, Turku, Finland

[40] Turku Univ Hosp, Turku, Finland

[41] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden

[42] Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Reg Vastra Gotaland, Gothenburg, Sweden

[43] Univ Lille, Inst Pasteur Lille, CNRS, European Genom Inst Diabet,UMR 8199, Lille, France

[44] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[45] Area Salut Menorca Ib Salut, Menorca, Spain

[46] Inst Invest Sanitaria Illes Balears IdISBa, Palma De Mallorca, Spain

[47] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England

[48] Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway

[49] Norwegian Inst Publ Hlth, Dept Genet & Bioinformat, Hlth Data & Digitalizat, Oslo, Norway

[50] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England

来源：

PLOS GENETICS | 2020年 / 16卷 / 10期

基金：

英国医学研究理事会; 欧洲研究理事会; 英国惠康基金;

关键词：

PROSTATE-SPECIFIC ANTIGEN; GENOME-WIDE ASSOCIATION; MENDELIAN RANDOMIZATION; CARDIOVASCULAR RISK; GENETIC-VARIATION; POOLED ANALYSIS; YOUNG-ADULTS; OBESITY; OVERWEIGHT; ADIPOSITY;

D O I：

10.1371/journal.pgen.1008718

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：26

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