Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable
Debbie A Lawlor,Nicholas J. Timpson,Nicholas J. Timpson,Roger M. Harbord,Sam D Leary,Andy R Ness,Mark I. McCarthy,Mark I. McCarthy,Timothy M. Frayling,Andrew T. Hattersley,George Davey Smith +10 more
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TLDR
Neither the parental comparisons nor the use of FTO genotype as an instrumental variable, suggest that greater maternal BMI during offspring development has a marked effect on offspring fat mass at age 9–11 y, which is unlikely to have driven the recent obesity epidemic.Abstract:
Background
The developmental overnutrition hypothesis suggests that greater maternal obesity during pregnancy results in increased offspring adiposity in later life. If true, this would result in the obesity epidemic progressing across generations irrespective of environmental or genetic changes. It is therefore important to robustly test this hypothesis.read more
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Cohort Profile: The Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort
Abigail Fraser,Corrie Macdonald-Wallis,Kate Tilling,Andy Boyd,Jean Golding,George Davey Smith,John Henderson,John Macleod,Lynn Molloy,Andy R Ness,S M Ring,Scott M. Nelson,Debbie A Lawlor +12 more
TL;DR: The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children.
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Developmental Origins of Health and Disease: Brief History of the Approach and Current Focus on Epigenetic Mechanisms
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References
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TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
ReportDOI
Instrumental variables regression with weak instruments
TL;DR: In this paper, the authors developed asymptotic distribution theory for instrumental variable regression when the partial correlation between the instruments and a single included endogenous variable is weak, here modeled as local to zero.
Journal ArticleDOI
A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity
Timothy M. Frayling,Nicholas J. Timpson,Michael N. Weedon,Eleftheria Zeggini,Eleftheria Zeggini,Eleftheria Zeggini,Rachel M. Freathy,Cecilia M. Lindgren,John R. B. Perry,Katherine S. Elliott,Katherine S. Elliott,Hana Lango,Nigel W. Rayner,Nigel W. Rayner,Nigel W. Rayner,Beverley M. Shields,Lorna W. Harries,Jeffrey C. Barrett,Jeffrey C. Barrett,Sian Ellard,Christopher J. Groves,Christopher J. Groves,Bridget A. Knight,Ann-Marie Patch,Andy R Ness,Shah Ebrahim,Debbie A Lawlor,Susan M. Ring,Yoav Ben-Shlomo,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Ulla Sovio,Ulla Sovio,Amanda J. Bennett,Amanda J. Bennett,David Melzer,Luigi Ferrucci,Ruth J. F. Loos,Inês Barroso,Nicholas J. Wareham,Fredrik Karpe,Fredrik Karpe,Katharine R. Owen,Katharine R. Owen,Lon R. Cardon,Mark Walker,Graham A. Hitman,Graham A. Hitman,Colin N. A. Palmer,Colin N. A. Palmer,Alex S. F. Doney,Alex S. F. Doney,Andrew D. Morris,George Davey Smith,Andrew T. Hattersley,Mark I. McCarthy +55 more
TL;DR: A genome-wide search for type 2 diabetes–susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI).
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‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?
George Davey Smith,Shah Ebrahim +1 more
TL;DR: Mendelian randomization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to understanding and preventing the adverse effects on human health of modifiable exposures.
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Childhood obesity: public-health crisis, common sense cure
TL;DR: In view of its rapid development in genetically stable populations, the childhood obesity epidemic can be primarily attributed to adverse environmental factors for which straightforward, if politically difficult, solutions exist.
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