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| PMID |
|
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| TITLE |
|
| Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study. |
|
| ABSTRACT |
|
| BACKGROUND |
NlmCategory: BACKGROUND |
| Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. MR using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis. |
| METHODS |
NlmCategory: METHODS |
| Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. MR using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis. Applying both population and within-sibship MR, we estimated the effects of genetic liability to educational attainment on body mass index (BMI), cigarette smoking, systolic blood pressure (SBP) and all-cause mortality. MR analyses used individual-level data on 72 932 siblings from UK Biobank and the Norwegian HUNT study, and summary-level data from a within-sibship Genome-wide Association Study including >140 000 individuals. |
| RESULTS |
NlmCategory: RESULTS |
| Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. MR using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis. Applying both population and within-sibship MR, we estimated the effects of genetic liability to educational attainment on body mass index (BMI), cigarette smoking, systolic blood pressure (SBP) and all-cause mortality. MR analyses used individual-level data on 72 932 siblings from UK Biobank and the Norwegian HUNT study, and summary-level data from a within-sibship Genome-wide Association Study including >140 000 individuals. Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant-outcome associations attenuated in the within-sibship model, but genetic variant-educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect. |
| CONCLUSIONS |
NlmCategory: CONCLUSIONS |
| Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. MR using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis. Applying both population and within-sibship MR, we estimated the effects of genetic liability to educational attainment on body mass index (BMI), cigarette smoking, systolic blood pressure (SBP) and all-cause mortality. MR analyses used individual-level data on 72 932 siblings from UK Biobank and the Norwegian HUNT study, and summary-level data from a within-sibship Genome-wide Association Study including >140 000 individuals. Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant-outcome associations attenuated in the within-sibship model, but genetic variant-educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect. These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders. |
| © The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2022/01/28 |
| accepted |
2023/05/12 |
| medline |
2023/06/10 15:14 |
| pubmed |
2023/06/10 15:14 |
| entrez |
2023/06/09 21:38 |
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| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Howe LJ |
|
Howe |
Laurence J |
LJ |
|
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. |
| Rasheed H |
|
Rasheed |
Humaira |
H |
|
Department of Medicine and Laboratory Sciences, University of Oslo, Oslo, Norway. |
| Jones PR |
|
Jones |
Paul R |
PR |
|
Department of Community Medicine and Global Health, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway. |
| Boomsma DI |
|
Boomsma |
Dorret I |
DI |
|
Amsterdam Public Health (APH) and Amsterdam Reproduction and Development (AR&D). |
| Evans DM |
|
Evans |
David M |
DM |
|
Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia. |
| Giannelis A |
|
Giannelis |
Alexandros |
A |
|
Department of Psychology, University of Minnesota, Minneapolis, MN, USA. |
| Hayward C |
|
Hayward |
Caroline |
C |
|
MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK. |
| Hopper JL |
|
Hopper |
John L |
JL |
|
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia. |
| Hughes A |
|
Hughes |
Amanda |
A |
|
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. |
| Lahtinen H |
|
Lahtinen |
Hannu |
H |
|
Population Research Unit, University of Helsinki, Helsinki, Finland. |
| Li S |
|
Li |
Shuai |
S |
|
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia. |
| Lind PA |
|
Lind |
Penelope A |
PA |
|
Faculty of Medicine, University of Queensland, Brisbane, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Martikainen P |
|
Martikainen |
Pekka |
P |
|
Department of Public Health Sciences, Stockholm University, Sweden. |
| Medland SE |
|
Medland |
Sarah E |
SE |
|
School of Psychology, University of Queensland, Brisbane, Australia. |
| Morris TT |
|
Morris |
Tim T |
TT |
|
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. |
| Nivard MG |
|
Nivard |
Michel G |
MG |
|
Department of Biological Psychology, Netherlands Twin Registry, Vrije Universiteit, Amsterdam, Netherlands. |
| Pingault JB |
|
Pingault |
Jean-Baptiste |
JB |
|
Department of Clinical, Educational and Health Psychology, University College London, London, UK. |
| Silventoinen K |
|
Silventoinen |
Karri |
K |
|
Population Research Unit, University of Helsinki, Helsinki, Finland. |
| Smith JA |
|
Smith |
Jennifer A |
JA |
|
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA. |
| Willoughby EA |
|
Willoughby |
Emily A |
EA |
|
Department of Psychology, University of Minnesota, Minneapolis, MN, USA. |
| Wilson JF |
|
Wilson |
James F |
JF |
|
Centre for Global Health Research, Usher Institute, University of Edinburgh, Teviot Place, Edinburgh, UK. |
|
Within Family Consortium |
|
|
|
|
|
| Åsvold BO |
|
Åsvold |
Bjørn Olav |
BO |
|
Department of Endocrinology, Clinic of Medicine, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. |
| Næss ØE |
|
Næss |
Øyvind E |
ŘE |
|
Norwegian Institute of Public Health, Oslo, Norway. |
| Davey Smith G |
|
Davey Smith |
George |
G |
|
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. |
| Kaprio J |
|
Kaprio |
Jaakko |
J |
|
Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland. |
| Brumpton B |
|
Brumpton |
Ben |
B |
|
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. |
| Davies NM |
|
Davies |
Neil M |
NM |
|
Department of Statistical Sciences, University College London, London, UK. |
|
| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Ahlskog |
Rafael |
R |
|
| Andreassen |
Ole A |
OA |
|
| Ask |
Helga |
H |
|
| Campbell |
Archie |
A |
|
| Cheesman |
Rosa |
R |
|
| Cho |
Yoonsu |
Y |
|
| Christensen |
Kaare |
K |
|
| Corfield |
Elizabeth C |
EC |
|
| Dahm |
Christina C |
CC |
|
| Havdahl |
Alexandra |
A |
|
| Hill |
William D |
WD |
|
| Kerr |
Shona M |
SM |
|
| Latvala |
Antti |
A |
|
| Nygaard |
Marianne |
M |
|
| Palviainen |
Teemu |
T |
|
| Pedersen |
Nancy L |
NL |
|
| Plomin |
Robert |
R |
|
| Southey |
Melissa C |
MC |
|
| Stoltenberg |
Camilla |
C |
|
|
| JOURNAL |
|
| VOLUME: |
| ISSUE: |
| TITLE: International journal of epidemiology |
| ISOABBREVIATION: Int J Epidemiol |
| YEAR: 2023 |
| MONTH: Jun |
| DAY: 09 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1464-3685 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
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| MEDLINETA: Int J Epidemiol |
| COUNTRY: England |
| ISSNLINKING: 0300-5771 |
| NLMUNIQUEID: 7802871 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| Mendelian randomization |
| Within-sibship |
| educational attainment |
| mortality |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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