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Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects
- Source :
- Nature genetics, vol 54, iss 5, Nature Genetics, Nature genetics, 54(5), 581-592. Nature Publishing Group, 2022, ' Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects ', Nature Genetics, vol. 54, no. 5, pp. 581-592 . https://doi.org/10.1038/s41588-022-01062-7, Howe, L J, Nivard, M G, Morris, T T, Hansen, A F, Rasheed, H, van der Zee, M D, Boomsma, D I, de Geus, E J C, Kweon, H, Koellinger, P D, Bartels, M, Davey Smith, G, Hayward, C, Brumpton, B, Hemani, G, Davies, N M & Social Science Genetic Association Consortium 2022, ' Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects ', Nature genetics, vol. 54, no. 5, pp. 581-592 . https://doi.org/10.1038/s41588-022-01062-7, Howe, L J, Nivard, M G, Morris, T T, Hansen, A F, Rasheed, H, Cho, Y, Chittoor, G, Ahlskog, R, Lind, P A, Palviainen, T, van der Zee, M D, Cheesman, R, Mangino, M, Wang, Y, Li, S, Klaric, L, Ratliff, S M, Bielak, L F, Nygaard, M, Giannelis, A, Willoughby, E A, Reynolds, C A, Balbona, J V, Andreassen, O A, Ask, H, Baras, A, Bauer, C R, Boomsma, D I, Campbell, A, Campbell, H, Chen, Z, Christofidou, P, Corfield, E, Dahm, C C, Dokuru, D R, Evans, L M, de Geus, E J C, Giddaluru, S, Gordon, S D, Harden, K P, Hill, W D, Hughes, A, Kerr, S M, Kim, Y, Kweon, H, Latvala, A, Lawlor, D A, Li, L, Lin, K, Christensen, K, Social Science Genetic Association Consortium & Within Family Consortium (Christina Dahm; member) 2022, ' Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects ', Nature Genetics, vol. 54, no. 5, pp. 581-592 . https://doi.org/10.1038/s41588-022-01062-7
- Publication Year :
- 2022
- Publisher :
- Nature Portfolio, 2022.
-
Abstract
- Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects. Within-sibship genome-wide association analyses using data from 178,076 siblings illustrate differences between population-based and within-sibship GWAS estimates for phenotypes influenced by demographic and indirect genetic effects.
- Subjects :
- Multifactorial Inheritance
Polymorphism, Single Nucleotide
Within Family Consortium
Medical and Health Sciences
Social Science Genetic Association Consortium
Genetics
Humans
2.1 Biological and endogenous factors
Polymorphism
Aetiology
Multifactorial Inheritance/genetics
Medicinsk genetik
Pediatric
Human Genome
1184 Genetics, developmental biology, physiology
Single Nucleotide
Mendelian Randomization Analysis
Biological Sciences
Polymorphism, Single Nucleotide/genetics
3142 Public health care science, environmental and occupational health
Phenotype
Mental health
Generic health relevance
Medical Genetics
Genome-Wide Association Study
Developmental Biology
Subjects
Details
- ISSN :
- 10614036
- Database :
- OpenAIRE
- Journal :
- Nature genetics, vol 54, iss 5, Nature Genetics, Nature genetics, 54(5), 581-592. Nature Publishing Group, 2022, ' Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects ', Nature Genetics, vol. 54, no. 5, pp. 581-592 . https://doi.org/10.1038/s41588-022-01062-7, Howe, L J, Nivard, M G, Morris, T T, Hansen, A F, Rasheed, H, van der Zee, M D, Boomsma, D I, de Geus, E J C, Kweon, H, Koellinger, P D, Bartels, M, Davey Smith, G, Hayward, C, Brumpton, B, Hemani, G, Davies, N M & Social Science Genetic Association Consortium 2022, ' Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects ', Nature genetics, vol. 54, no. 5, pp. 581-592 . https://doi.org/10.1038/s41588-022-01062-7, Howe, L J, Nivard, M G, Morris, T T, Hansen, A F, Rasheed, H, Cho, Y, Chittoor, G, Ahlskog, R, Lind, P A, Palviainen, T, van der Zee, M D, Cheesman, R, Mangino, M, Wang, Y, Li, S, Klaric, L, Ratliff, S M, Bielak, L F, Nygaard, M, Giannelis, A, Willoughby, E A, Reynolds, C A, Balbona, J V, Andreassen, O A, Ask, H, Baras, A, Bauer, C R, Boomsma, D I, Campbell, A, Campbell, H, Chen, Z, Christofidou, P, Corfield, E, Dahm, C C, Dokuru, D R, Evans, L M, de Geus, E J C, Giddaluru, S, Gordon, S D, Harden, K P, Hill, W D, Hughes, A, Kerr, S M, Kim, Y, Kweon, H, Latvala, A, Lawlor, D A, Li, L, Lin, K, Christensen, K, Social Science Genetic Association Consortium & Within Family Consortium (Christina Dahm; member) 2022, ' Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects ', Nature Genetics, vol. 54, no. 5, pp. 581-592 . https://doi.org/10.1038/s41588-022-01062-7
- Accession number :
- edsair.doi.dedup.....c79333b5ded2e2eaeb727a1345dda5ae