ArticleAmerican journal of human genetics2013
Inference of the genetic architecture underlying BMI and height with the use of 20,240 sibling pairs.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-wide association study using family-based cohorts identifies the WLS and CCDC170/ESR1 loci as associated with bone mineral density.BMC genomics · 2016Pooled it
- The association between parental BMI and offspring adiposity: A genetically informed analysis of trios.PLoS genetics · 2025Article
- Sequence-based GWAS in 180,000 German Holstein cattle reveals new candidate variants for milk production traits.Genetics, selection, evolution : GSE · 2025Article
- Genetic architecture reconciles linkage and association studies of complex traits.Nature genetics · 2024Article
- Genetic analysis of selection bias in a natural experiment: Investigating in-utero famine effects on elevated body mass index in the Dutch Hunger Winter Families Study.American journal of epidemiology · 2024Article
- Direct and Indirect Genetic Effects on Aggression.Biological psychiatry global open science · 2023Article
- Harnessing male germline epigenomics for the genetic improvement in cattle.Journal of animal science and biotechnology · 2023Review
- Annual Research Review: Towards a deeper understanding of nature and nurture: combining family-based quasi-experimental methods with genomic data.Journal of child psychology and psychiatry, and allied disciplines · 2023Review
- Genetic heterogeneity in cardiovascular disease across ancestries: Insights for mechanisms and therapeutic intervention.Cambridge prisms. Precision medicine · 2023Review
- Evidence for correlations between BMI-associated SNPs and circRNAs.Scientific reports · 2022Article
- Clinical Profiles and Genetic Spectra of 814 Chinese Children With Short Stature.The Journal of clinical endocrinology and metabolism · 2022Article
- A statistical boosting framework for polygenic risk scores based on large-scale genotype data.Frontiers in genetics · 2022Article
- Phantom epistasis between unlinked loci.Nature · 2021Article
- The Augmented Classical Twin Design: Incorporating Genome-Wide Identity by Descent Sharing Into Twin Studies in Order to Model Violations of the Equal Environments Assumption.Behavior genetics · 2021Article
- The Evolutionary History of Common Genetic Variants Influencing Human Cortical Surface Area.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Phenotypic covariance across the entire spectrum of relatedness for 86 billion pairs of individuals.Nature communications · 2021Article
- Non-linear interaction between physical activity and polygenic risk score of body mass index in Danish and Russian populations.PloS one · 2021Article
- High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- A genome-wide association study of childhood adiposity and blood lipids.Wellcome open research · 2021Article
- Genetic information from discordant sibling pairs points to ESRP2 as a candidate trans-acting regulator of the CF modifier gene SCNN1B.Scientific reports · 2020Article
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23 authors.
Funding
Abstract
Evidence that complex traits are highly polygenic has been presented by population-based genome-wide association studies (GWASs) through the identification of many significant variants, as well as by family-based de novo sequencing studies indicating that several traits have a large mutational target size. Here, using a third study design, we show results consistent with extreme polygenicity for body mass index (BMI) and height. On a sample of 20,240 siblings (from 9,570 nuclear families), we used a within-family method to obtain narrow-sense heritability estimates of 0.42 (SE = 0.17, p = 0.01) and 0.69 (SE = 0.14, p = 6 × 10(-)(7)) for BMI and height, respectively, after adjusting for covariates. The genomic inflation factors from locus-specific linkage analysis were 1.69 (SE = 0.21, p = 0.04) for BMI and 2.18 (SE = 0.21, p = 2 × 10(-10)) for height. This inflation is free of confounding and congruent with polygenicity, consistent with observations of ever-increasing genomic-inflation factors from GWASs with large sample sizes, implying that those signals are due to true genetic signals across the genome rather than population stratification. We also demonstrate that the distribution of the observed test statistics is consistent with both rare and common variants underlying a polygenic architecture and that previous reports of linkage signals in complex traits are probably a consequence of polygenic architecture rather than the segregation of variants with large effects. The convergent empirical evidence from GWASs, de novo studies, and within-family segregation implies that family-based sequencing studies for complex traits require very large sample sizes because the effects of causal variants are small on average.
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