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Published in: European Journal of Epidemiology 3/2019

Open Access 01-03-2019 | CONSORTIUM

The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia: design, results and future prospects

Authors: Christel M. Middeldorp, Janine F. Felix, Anubha Mahajan, Mark I. McCarthy, EArly Genetics Lifecourse Epidemiology (EAGLE) consortium, Early Growth Genetics (EGG) consortium

Published in: European Journal of Epidemiology | Issue 3/2019

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Abstract

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Literature
1.
go back to reference Global Burden of Disease Pediatrics Collaboration. Global and national burden of diseases and injuries among children and adolescents between 1990 and 2013: findings from the global burden of disease 2013 study. JAMA Pediatr. 2016;170:267–87.CrossRef Global Burden of Disease Pediatrics Collaboration. Global and national burden of diseases and injuries among children and adolescents between 1990 and 2013: findings from the global burden of disease 2013 study. JAMA Pediatr. 2016;170:267–87.CrossRef
2.
go back to reference Nadeau KJ, Maahs DM, Daniels SR, Eckel RH. Childhood obesity and cardiovascular disease: links and prevention strategies. Nat Rev Cardiol. 2011;8:513–25.CrossRefPubMedPubMedCentral Nadeau KJ, Maahs DM, Daniels SR, Eckel RH. Childhood obesity and cardiovascular disease: links and prevention strategies. Nat Rev Cardiol. 2011;8:513–25.CrossRefPubMedPubMedCentral
3.
go back to reference Costello EJ, Maughan B. Annual research review: optimal outcomes of child and adolescent mental illness. J Child Psychol Psychiatry. 2015;56:324–41.CrossRefPubMed Costello EJ, Maughan B. Annual research review: optimal outcomes of child and adolescent mental illness. J Child Psychol Psychiatry. 2015;56:324–41.CrossRefPubMed
4.
go back to reference Maibing CF, Pedersen CB, Benros ME, Mortensen PB, Dalsgaard S, Nordentoft M. Risk of schizophrenia increases after all child and adolescent psychiatric disorders: a nationwide study. Schizophr Bull. 2015;41:963–70.CrossRefPubMed Maibing CF, Pedersen CB, Benros ME, Mortensen PB, Dalsgaard S, Nordentoft M. Risk of schizophrenia increases after all child and adolescent psychiatric disorders: a nationwide study. Schizophr Bull. 2015;41:963–70.CrossRefPubMed
6.
go back to reference O’Donnell KJ, Meaney MJ. Fetal origins of mental health: the developmental origins of health and disease hypothesis. Am J Psychiatry. 2017;174:319–28.CrossRefPubMed O’Donnell KJ, Meaney MJ. Fetal origins of mental health: the developmental origins of health and disease hypothesis. Am J Psychiatry. 2017;174:319–28.CrossRefPubMed
8.
go back to reference Polderman TJ, Benyamin B, de Leeuw CA, et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet. 2015;47:702.CrossRefPubMed Polderman TJ, Benyamin B, de Leeuw CA, et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet. 2015;47:702.CrossRefPubMed
9.
go back to reference Hayiou-Thomas ME, Dale PS, Plomin R. The etiology of variation in language skills changes with development: a longitudinal twin study of language from 2 to 12 years. Dev Sci. 2012;15:233–49.CrossRefPubMed Hayiou-Thomas ME, Dale PS, Plomin R. The etiology of variation in language skills changes with development: a longitudinal twin study of language from 2 to 12 years. Dev Sci. 2012;15:233–49.CrossRefPubMed
10.
go back to reference Kan KJ, Dolan CV, Nivard MG, et al. Genetic and environmental stability in attention problems across the lifespan: evidence from the Netherlands twin register. J Am Acad Child Adolesc Psychiatry. 2013;52:12–25.CrossRefPubMed Kan KJ, Dolan CV, Nivard MG, et al. Genetic and environmental stability in attention problems across the lifespan: evidence from the Netherlands twin register. J Am Acad Child Adolesc Psychiatry. 2013;52:12–25.CrossRefPubMed
11.
go back to reference Nivard MG, Dolan CV, Kendler KS, et al. Stability in symptoms of anxiety and depression as a function of genotype and environment: a longitudinal twin study from ages 3 to 63 years. Psychol Med. 2015;45:1039–49.CrossRefPubMed Nivard MG, Dolan CV, Kendler KS, et al. Stability in symptoms of anxiety and depression as a function of genotype and environment: a longitudinal twin study from ages 3 to 63 years. Psychol Med. 2015;45:1039–49.CrossRefPubMed
12.
go back to reference Silventoinen K, Kaprio J, Yokoyama Y. Genetic regulation of pre-pubertal development of body mass index: a longitudinal study of Japanese twin boys and girls. Behav Genet. 2011;41:234–41.CrossRefPubMed Silventoinen K, Kaprio J, Yokoyama Y. Genetic regulation of pre-pubertal development of body mass index: a longitudinal study of Japanese twin boys and girls. Behav Genet. 2011;41:234–41.CrossRefPubMed
13.
go back to reference Wichers M, Gardner C, Maes HH, Lichtenstein P, Larsson H, Kendler KS. Genetic innovation and stability in externalizing problem behavior across development: a multi-informant twin study. Behav Genet. 2013;43:191–201.CrossRefPubMed Wichers M, Gardner C, Maes HH, Lichtenstein P, Larsson H, Kendler KS. Genetic innovation and stability in externalizing problem behavior across development: a multi-informant twin study. Behav Genet. 2013;43:191–201.CrossRefPubMed
15.
go back to reference 1000 Genomes Project Consortium, Auton A, Brooks LD, et al. A global reference for human genetic variation. Nature. 2015;526:68–74.CrossRef 1000 Genomes Project Consortium, Auton A, Brooks LD, et al. A global reference for human genetic variation. Nature. 2015;526:68–74.CrossRef
17.
go back to reference Beaumont RN, Warrington NM, Cavadino A, et al. Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics. Hum Mol Genet. 2018;27:742–56.CrossRefPubMedPubMedCentral Beaumont RN, Warrington NM, Cavadino A, et al. Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics. Hum Mol Genet. 2018;27:742–56.CrossRefPubMedPubMedCentral
18.
go back to reference Benke KS, Nivard MG, Velders FP, et al. A genome-wide association meta-analysis of preschool internalizing problems. J Am Acad Child Adolesc Psychiatry. 2014;53(667–76):e7. Benke KS, Nivard MG, Velders FP, et al. A genome-wide association meta-analysis of preschool internalizing problems. J Am Acad Child Adolesc Psychiatry. 2014;53(667–76):e7.
19.
go back to reference Bonnelykke K, Matheson MC, Pers TH, et al. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. Nat Genet. 2013;45:902–6.CrossRefPubMedPubMedCentral Bonnelykke K, Matheson MC, Pers TH, et al. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. Nat Genet. 2013;45:902–6.CrossRefPubMedPubMedCentral
20.
go back to reference Bouzigon E, Nadif R, Thompson EE, et al. A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults. Clin Exp Allergy. 2015;45:797–806.CrossRefPubMedPubMedCentral Bouzigon E, Nadif R, Thompson EE, et al. A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults. Clin Exp Allergy. 2015;45:797–806.CrossRefPubMedPubMedCentral
21.
22.
go back to reference Bustamante M, Standl M, Bassat Q, et al. A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways. Hum Mol Genet. 2016;25:4127–42.CrossRefPubMedPubMedCentral Bustamante M, Standl M, Bassat Q, et al. A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways. Hum Mol Genet. 2016;25:4127–42.CrossRefPubMedPubMedCentral
23.
go back to reference Cousminer DL, Berry DJ, Timpson NJ, et al. Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. Hum Mol Genet. 2013;22:2735–47.CrossRefPubMedPubMedCentral Cousminer DL, Berry DJ, Timpson NJ, et al. Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. Hum Mol Genet. 2013;22:2735–47.CrossRefPubMedPubMedCentral
24.
go back to reference Cousminer DL, Stergiakouli E, Berry DJ, et al. Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty. Hum Mol Genet. 2014;23:4452–64.CrossRefPubMedPubMedCentral Cousminer DL, Stergiakouli E, Berry DJ, et al. Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty. Hum Mol Genet. 2014;23:4452–64.CrossRefPubMedPubMedCentral
26.
go back to reference Felix JF, Bradfield JP, Monnereau C, et al. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. Hum Mol Genet. 2016;15:389–403.CrossRef Felix JF, Bradfield JP, Monnereau C, et al. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. Hum Mol Genet. 2016;15:389–403.CrossRef
27.
go back to reference Freathy RM, Mook-Kanamori DO, Sovio U, et al. Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nat Genet. 2010;42:430–5.CrossRefPubMedPubMedCentral Freathy RM, Mook-Kanamori DO, Sovio U, et al. Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nat Genet. 2010;42:430–5.CrossRefPubMedPubMedCentral
28.
29.
go back to reference Horikoshi M, Yaghootkar H, Mook-Kanamori DO, et al. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism. Nat Genet. 2013;45:76–82.CrossRefPubMed Horikoshi M, Yaghootkar H, Mook-Kanamori DO, et al. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism. Nat Genet. 2013;45:76–82.CrossRefPubMed
30.
31.
go back to reference Marinelli M, Pappa I, Bustamante M, et al. Heritability and genome-wide association analyses of sleep duration in children: the EAGLE consortium. Sleep. 2016;39:1859–69.CrossRefPubMedPubMedCentral Marinelli M, Pappa I, Bustamante M, et al. Heritability and genome-wide association analyses of sleep duration in children: the EAGLE consortium. Sleep. 2016;39:1859–69.CrossRefPubMedPubMedCentral
32.
go back to reference Middeldorp CM, Hammerschlag AR, Ouwens KG, et al. A genome-wide association meta-analysis of attention-deficit/hyperactivity disorder symptoms in population-based pediatric cohorts. J Am Acad Child Adolesc Psychiatry. 2016;55(896–905):e6. Middeldorp CM, Hammerschlag AR, Ouwens KG, et al. A genome-wide association meta-analysis of attention-deficit/hyperactivity disorder symptoms in population-based pediatric cohorts. J Am Acad Child Adolesc Psychiatry. 2016;55(896–905):e6.
33.
go back to reference Pappa I, St Pourcain B, Benke K, et al. A genome-wide approach to children’s aggressive behavior: the EAGLE consortium. Am J Med Genet B Neuropsychiatr Genet. 2016;171:562–72.CrossRefPubMed Pappa I, St Pourcain B, Benke K, et al. A genome-wide approach to children’s aggressive behavior: the EAGLE consortium. Am J Med Genet B Neuropsychiatr Genet. 2016;171:562–72.CrossRefPubMed
34.
go back to reference Parmar PG, Taal HR, Timpson NJ, et al. International genome-wide association study consortium identifies novel loci associated with blood pressure in children and adolescents. Circ Cardiovasc Genet. 2016;9:266–78.CrossRefPubMedPubMedCentral Parmar PG, Taal HR, Timpson NJ, et al. International genome-wide association study consortium identifies novel loci associated with blood pressure in children and adolescents. Circ Cardiovasc Genet. 2016;9:266–78.CrossRefPubMedPubMedCentral
35.
go back to reference Paternoster L, Standl M, Chen CM, et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat Genet. 2012;44:187–92.CrossRef Paternoster L, Standl M, Chen CM, et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat Genet. 2012;44:187–92.CrossRef
36.
go back to reference Paternoster L, Standl M, Waage J, et al. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet. 2015;47:1449–56.CrossRefPubMedPubMedCentral Paternoster L, Standl M, Waage J, et al. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet. 2015;47:1449–56.CrossRefPubMedPubMedCentral
37.
38.
go back to reference Sovio U, Mook-Kanamori DO, Warrington NM, et al. Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: the complex nature of genetic association through growth and development. PLoS Genet. 2011;7:e1001307.CrossRefPubMedPubMedCentral Sovio U, Mook-Kanamori DO, Warrington NM, et al. Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: the complex nature of genetic association through growth and development. PLoS Genet. 2011;7:e1001307.CrossRefPubMedPubMedCentral
39.
go back to reference St Pourcain B, Cents RA, Whitehouse AJ, et al. Common variation near ROBO2 is associated with expressive vocabulary in infancy. Nat Commun. 2014;5:4831.CrossRefPubMed St Pourcain B, Cents RA, Whitehouse AJ, et al. Common variation near ROBO2 is associated with expressive vocabulary in infancy. Nat Commun. 2014;5:4831.CrossRefPubMed
40.
41.
go back to reference Taal HR, Verwoert GC, Demirkan A, et al. Genome-wide profiling of blood pressure in adults and children. Hypertension. 2012;59:241–7.CrossRefPubMed Taal HR, Verwoert GC, Demirkan A, et al. Genome-wide profiling of blood pressure in adults and children. Hypertension. 2012;59:241–7.CrossRefPubMed
42.
go back to reference Tyrrell J, Richmond RC, Palmer TM, et al. Genetic evidence for causal relationships between maternal obesity-related traits and birth weight. JAMA. 2016;315:1129–40.CrossRefPubMedPubMedCentral Tyrrell J, Richmond RC, Palmer TM, et al. Genetic evidence for causal relationships between maternal obesity-related traits and birth weight. JAMA. 2016;315:1129–40.CrossRefPubMedPubMedCentral
43.
go back to reference van der Valk RJ, Duijts L, Timpson NJ, et al. Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants. J Allergy Clin Immunol. 2014;134:46–55.CrossRefPubMed van der Valk RJ, Duijts L, Timpson NJ, et al. Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants. J Allergy Clin Immunol. 2014;134:46–55.CrossRefPubMed
44.
go back to reference van der Valk RJ, Kreiner-Moller E, Kooijman MN, et al. A novel common variant in DCST2 is associated with length in early life and height in adulthood. Hum Mol Genet. 2015;24:1155–68.CrossRefPubMed van der Valk RJ, Kreiner-Moller E, Kooijman MN, et al. A novel common variant in DCST2 is associated with length in early life and height in adulthood. Hum Mol Genet. 2015;24:1155–68.CrossRefPubMed
45.
go back to reference Warrington NM, Richmond R, Fenstra B, et al. Maternal and fetal genetic contribution to gestational weight gain. Int J Obes (Lond.). 2017;42:775–84.CrossRef Warrington NM, Richmond R, Fenstra B, et al. Maternal and fetal genetic contribution to gestational weight gain. Int J Obes (Lond.). 2017;42:775–84.CrossRef
46.
go back to reference Bulik-Sullivan BK, Loh PR, Finucane HK, et al. LD score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet. 2015;47:291–5.CrossRefPubMedPubMedCentral Bulik-Sullivan BK, Loh PR, Finucane HK, et al. LD score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet. 2015;47:291–5.CrossRefPubMedPubMedCentral
47.
go back to reference Zheng J, Erzurumluoglu AM, Elsworth BL, et al. LD hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics. 2017;33:272–9.CrossRefPubMed Zheng J, Erzurumluoglu AM, Elsworth BL, et al. LD hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics. 2017;33:272–9.CrossRefPubMed
48.
go back to reference Warrington NM, Freathy RM, Neale MC, Evans DM. Using structural equation modelling to jointly estimate maternal and fetal effects on birthweight in the UK Biobank. Int J Epidemiol. 2018;47:1229–41.CrossRefPubMedPubMedCentral Warrington NM, Freathy RM, Neale MC, Evans DM. Using structural equation modelling to jointly estimate maternal and fetal effects on birthweight in the UK Biobank. Int J Epidemiol. 2018;47:1229–41.CrossRefPubMedPubMedCentral
49.
go back to reference Eaves LJ, Pourcain BS, Smith GD, York TP, Evans DM. Resolving the effects of maternal and offspring genotype on dyadic outcomes in genome wide complex trait analysis (“M-GCTA”). Behav Genet. 2014;44:445–55.CrossRefPubMedPubMedCentral Eaves LJ, Pourcain BS, Smith GD, York TP, Evans DM. Resolving the effects of maternal and offspring genotype on dyadic outcomes in genome wide complex trait analysis (“M-GCTA”). Behav Genet. 2014;44:445–55.CrossRefPubMedPubMedCentral
50.
go back to reference Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27:1133–63.CrossRefPubMed Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27:1133–63.CrossRefPubMed
51.
go back to reference Lawlor D, Richmond R, Warrington N, et al. Using Mendelian randomization to determine causal effects of maternal pregnancy (intrauterine) exposures on offspring outcomes: sources of bias and methods for assessing them. Wellcome Open Res. 2017;2:11.CrossRefPubMedPubMedCentral Lawlor D, Richmond R, Warrington N, et al. Using Mendelian randomization to determine causal effects of maternal pregnancy (intrauterine) exposures on offspring outcomes: sources of bias and methods for assessing them. Wellcome Open Res. 2017;2:11.CrossRefPubMedPubMedCentral
52.
go back to reference Nivard MG, Gage SH, Hottenga JJ, et al. Genetic overlap between schizophrenia and developmental psychopathology: longitudinal and multivariate polygenic risk prediction of common psychiatric traits during development. Schizophr Bull. 2017;43:1197–207.CrossRefPubMedPubMedCentral Nivard MG, Gage SH, Hottenga JJ, et al. Genetic overlap between schizophrenia and developmental psychopathology: longitudinal and multivariate polygenic risk prediction of common psychiatric traits during development. Schizophr Bull. 2017;43:1197–207.CrossRefPubMedPubMedCentral
53.
go back to reference van der Sluis S, Posthuma D, Nivard MG, Verhage M, Dolan CV. Power in GWAS: lifting the curse of the clinical cut-off. Mol Psychiatry. 2013;18:2–3.CrossRefPubMed van der Sluis S, Posthuma D, Nivard MG, Verhage M, Dolan CV. Power in GWAS: lifting the curse of the clinical cut-off. Mol Psychiatry. 2013;18:2–3.CrossRefPubMed
54.
go back to reference Nivard MG, Gage SH, Hottenga JJ, et al. Genetic overlap between schizophrenia and developmental psychopathology: longitudinal and multivariate polygenic risk prediction of common psychiatric traits during development. Schizophr Bull. 2017;43:1197–207.CrossRefPubMedPubMedCentral Nivard MG, Gage SH, Hottenga JJ, et al. Genetic overlap between schizophrenia and developmental psychopathology: longitudinal and multivariate polygenic risk prediction of common psychiatric traits during development. Schizophr Bull. 2017;43:1197–207.CrossRefPubMedPubMedCentral
55.
go back to reference Felix JF, Joubert BR, Baccarelli AA, et al. Cohort profile: pregnancy and childhood epigenetics (PACE) consortium. Int J Epidemiol. 2018;47:22u–3u.CrossRef Felix JF, Joubert BR, Baccarelli AA, et al. Cohort profile: pregnancy and childhood epigenetics (PACE) consortium. Int J Epidemiol. 2018;47:22u–3u.CrossRef
Metadata
Title
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia: design, results and future prospects
Authors
Christel M. Middeldorp
Janine F. Felix
Anubha Mahajan
Mark I. McCarthy
EArly Genetics Lifecourse Epidemiology (EAGLE) consortium
Early Growth Genetics (EGG) consortium
Publication date
01-03-2019
Publisher
Springer Netherlands
Published in
European Journal of Epidemiology / Issue 3/2019
Print ISSN: 0393-2990
Electronic ISSN: 1573-7284
DOI
https://doi.org/10.1007/s10654-019-00502-9

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