Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

被引：321

作者：

Warrington, Nicole M. ^{[1
,175
]}

Beaumont, Robin N. ^{[2
,175
]}

Horikoshi, Momoko ^{[3
,4
,5
,175
]}

Day, Felix R. ^{[6
,175
]}

Helgeland, Oyvind ^{[7
,8
,9
,175
]}

Laurin, Charles ^{[10
,11
]}

Bacelis, Jonas ^{[12
]}

Peng, Shouneng ^{[13
,14
]}

Hao, Ke ^{[13
,14
]}

Feenstra, Bjarke ^{[15
]}

Wood, Andrew R. ^{[2
]}

Mahajan, Anubha ^{[4
,5
]}

Tyrrell, Jessica ^{[2
,16
]}

Robertson, Neil R. ^{[4
,5
]}

Rayner, N. William ^{[4
,5
,17
]}

Qiao, Zhen ^{[1
]}

Moen, Gunn-Helen ^{[18
,19
]}

Vaudel, Marc ^{[7
]}

Marsit, Carmen J. ^{[20
]}

Chen, Jia ^{[21
]}

Nodzenski, Michael ^{[22
]}

Schnurr, Theresia M. ^{[23
]}

Zafarmand, Mohammad H. ^{[24
,25
]}

Bradfield, Jonathan P. ^{[26
,27
]}

Grarup, Niels ^{[23
]}

Kooijman, Marjolein N. ^{[28
,29
,30
]}

Li-Gao, Ruifang ^{[31
]}

Geller, Frank ^{[15
]}

Ahluwalia, Tarunveer S. ^{[23
,32
,33
]}

Paternoster, Lavinia ^{[10
]}

Rueedi, Rico ^{[34
,35
]}

Huikari, Ville ^{[36
]}

Hottenga, Jouke-Jan ^{[37
,38
,39
]}

Lyytikainen, Leo-Pekka ^{[40
,41
]}

Cavadino, Alana ^{[42
,43
]}

Metrustry, Sarah ^{[44
]}

Cousminer, Diana L. ^{[45
,46
]}

Wu, Ying ^{[47
]}

Thiering, Elisabeth ^{[48
,49
]}

Wang, Carol A. ^{[50
]}

Have, Christian T. ^{[23
]}

Vilor-Tejedor, Natalia ^{[51
,52
]}

Joshi, Peter K. ^{[53
]}

Painter, Jodie N. ^{[54
]}

Ntalla, Ioanna ^{[55
]}

Myhre, Ronny ^{[56
]}

Pitkanen, Niina ^{[57
]}

van Leeuwen, Elisabeth M. ^{[29
]}

Joro, Raimo ^{[58
]}

Lagou, Vasiliki ^{[4
,59
,60
]}

机构：

[1] Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia

[2] Univ Exeter, Inst Biomed & Clin Sci, Royal Devon & Exeter Hosp, Coll Med & Hlth, Exeter, Devon, England

[3] RIKEN, Lab Endocrinol Metab & Kidney Dis, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

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

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

[6] Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit, Cambridge, England

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

[8] Haukeland Hosp, Dept Pediat, Bergen, Norway

[9] Norwegian Inst Publ Hlth, Dept Genet & Bioinformat, Domain Hlth Data & Digitalisat, Oslo, Norway

[10] Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Bristol, Avon, England

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

[12] Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Gothenburg, Sweden

[13] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[14] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA

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

[16] Univ Exeter, European Ctr Environm & Human Hlth, Truro, England

[17] Wellcome Sanger Inst, Hinxton, England

[18] Oslo Univ Hosp, Dept Endocrinol Morbid Obes & Prevent Med, Oslo, Norway

[19] Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway

[20] Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, Atlanta, GA 30322 USA

[21] Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA

[22] Northwestern Univ, Feinberg Sch Med, Div Biostat, Dept Prevent Med, Chicago, IL 60611 USA

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

[24] Univ Amsterdam, Acad Med Ctr, Amsterdam UMC, Dept Publ Hlth,Amsterdam Publ Hlth Res Inst, Amsterdam, Netherlands

[25] Univ Amsterdam, Acad Med Ctr, Amsterdam UMC, Dept Clin Epidemiol Biostat & Bioinformat,Amsterd, Amsterdam, Netherlands

[26] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA

[27] Quantinuum Res, San Diego, CA USA

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

[29] Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands

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

[31] Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands

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

[33] Steno Diabet Ctr Copenhagen, Gentofte, Denmark

[34] Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland

[35] Swiss Inst Bioinformat, Lausanne, Switzerland

[36] Univ Oulu, Ctr Life Course Hlth Res, Fac Med, Oulu, Finland

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

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

[39] Amsterdam Publ Hlth, Amsterdam, Netherlands

[40] Fimlab Labs, Dept Clin Chem, Tampere, Finland

[41] Tampere Univ, Fac Med & Hlth Technol, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland

[42] Univ Auckland, Sch Populat Hlth, Sect Epidemiol & Biostat, Auckland, New Zealand

[43] UCL, UCL Great Ormond St Inst Child Hlth, Populat Policy & Practice, London, England

[44] Kings Coll London, St Thomas Hosp, Dept Twin Res, London, England

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

[46] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA

[47] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA

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

[49] Univ Munich, Med Ctr, Dr von Hauner Childrens Hosp, Div Metab & Nutr Med, Munich, Germany

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

来源：

NATURE GENETICS | 2019年 / 51卷 / 05期

关键词：

LD SCORE REGRESSION; MENDELIAN RANDOMIZATION; DIABETES-MELLITUS; BLOOD-PRESSURE; ASSOCIATION; ORIGINS; GROWTH; LIFE; PREGNANCY; DISEASE;

D O I：

10.1038/s41588-019-0403-1

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

引用

页码：804 / +

页数：17

共 50 条

[1] Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors
Nicole M. Warrington
Robin N. Beaumont
Momoko Horikoshi
Felix R. Day
Øyvind Helgeland
Charles Laurin
Jonas Bacelis
Shouneng Peng
Ke Hao
Bjarke Feenstra
Andrew R. Wood
Anubha Mahajan
Jessica Tyrrell
Neil R. Robertson
N. William Rayner
Zhen Qiao
Gunn-Helen Moen
Marc Vaudel
Carmen J. Marsit
Jia Chen
Michael Nodzenski
Theresia M. Schnurr
Mohammad H. Zafarmand
Jonathan P. Bradfield
Niels Grarup
Marjolein N. Kooijman
Ruifang Li-Gao
Frank Geller
Tarunveer S. Ahluwalia
Lavinia Paternoster
Rico Rueedi
Ville Huikari
Jouke-Jan Hottenga
Leo-Pekka Lyytikäinen
Alana Cavadino
Sarah Metrustry
Diana L. Cousminer
Ying Wu
Elisabeth Thiering
Carol A. Wang
Christian T. Have
Natalia Vilor-Tejedor
Peter K. Joshi
Jodie N. Painter
Ioanna Ntalla
Ronny Myhre
Niina Pitkänen
Elisabeth M. van Leeuwen
Raimo Joro
Vasiliki Lagou
[J]. Nature Genetics, 2019, 51 : 804 - 814
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