Dataset Information

Dominant Genetic Variation and Missing Heritability for Human Complex Traits: Insights from Twin versus Genome-wide Common SNP Models.

ABSTRACT: In order to further illuminate the potential role of dominant genetic variation in the "missing heritability" debate, we investigated the additive (narrow-sense heritability, h(2)) and dominant (?(2)) genetic variance for 18 human complex traits. Within the same study base (10,682 Swedish twins), we calculated and compared the estimates from classic twin-based structural equation model with SNP-based genomic-relatedness-matrix restricted maximum likelihood [GREML(d)] method. Contributions of ?(2) were evident for 14 traits in twin models (average ?(2)twin = 0.25, range 0.14-0.49), two of which also displayed significant ?(2) in the GREMLd analyses (triglycerides ?(2)SNP = 0.28 and waist circumference ?(2)SNP = 0.19). On average, the proportion of h(2)SNP/h(2)twin was 70% for ADE-fitted traits (for which the best-fitting model included additive and dominant genetic and unique environmental components) and 31% for AE-fitted traits (for which the best-fitting model included additive genetic and unique environmental components). Independent evidence for contribution from shared environment, also in ADE-fitted traits, was obtained from self-reported within-pair contact frequency and age at separation. We conclude that despite the fact that additive genetics appear to constitute the bulk of genetic influences for most complex traits, dominant genetic variation might often be masked by shared environment in twin and family studies and might therefore have a more prominent role than what family-based estimates often suggest. The risk of erroneously attributing all inherited genetic influences (additive and dominant) to the h(2) in too-small twin studies might also lead to exaggerated "missing heritability" (the proportion of h(2) that remains unexplained by SNPs).

SUBMITTER: Chen X

PROVIDER: S-EPMC4667127 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dominant Genetic Variation and Missing Heritability for Human Complex Traits: Insights from Twin versus Genome-wide Common SNP Models.

Chen Xu X Kuja-Halkola Ralf R Rahman Iffat I Arpegård Johannes J Viktorin Alexander A Karlsson Robert R Hägg Sara S Svensson Per P Pedersen Nancy L NL Magnusson Patrik K E PK

American journal of human genetics 20151101 5

In order to further illuminate the potential role of dominant genetic variation in the "missing heritability" debate, we investigated the additive (narrow-sense heritability, h(2)) and dominant (δ(2)) genetic variance for 18 human complex traits. Within the same study base (10,682 Swedish twins), we calculated and compared the estimates from classic twin-based structural equation model with SNP-based genomic-relatedness-matrix restricted maximum likelihood [GREML(d)] method. Contributions of δ(2 ...[more]

PMID: 26544805

Similar Datasets

Project description:BackgroundGenetics have a strong influence on calcified atherosclerotic plaques; however, data regarding the heritability of noncalcified plaque volume are scarce. We aimed to evaluate genetic versus environmental influences on calcium (coronary artery calcification) score, noncalcified and calcified plaque volumes by coronary computed tomography angiography in adult twin pairs without known coronary artery disease.MethodsIn the prospective BUDAPEST-GLOBAL (Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions) classical twin study, we analyzed twin pairs without known coronary artery disease. All twins underwent coronary computed tomography angiography to assess coronary atherosclerotic plaque volumes. Structural equation models were used to quantify the contribution of additive genetic, common environmental, and unique environmental components to plaque volumes adjusted for age, gender, or atherosclerotic cardiovascular disease risk estimate and statin use.ResultsWe included 196 twins (mean age±SD, 56±9 years, 63.3% females), 120 monozygotic and 76 same-gender dizygotic pairs. Using structural equation models, noncalcified plaque volume was predominantly determined by environmental factors (common environment, 63% [95% CI, 56%-67%], unique environment, 37% [95% CI, 33%-44%]), while coronary artery calcification score and calcified plaque volumes had a relatively strong genetic heritability (additive genetic, 58% [95% CI, 50%-66%]; unique environmental, 42% [95% CI, 34%-50%] and additive genetic, 78% [95% CI, 73%-80%]; unique environmental, 22% [95% CI, 20%-27%]), respectively.ConclusionsNoncalcified plaque volume is mainly influenced by shared environmental factors, whereas coronary artery calcification score and calcified plaque volume are more determined by genetics. These findings emphasize the importance of early lifestyle interventions in preventing coronary plaque formation.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT01738828.

Dataset Information

Dominant Genetic Variation and Missing Heritability for Human Complex Traits: Insights from Twin versus Genome-wide Common SNP Models.

Publications

Dominant Genetic Variation and Missing Heritability for Human Complex Traits: Insights from Twin versus Genome-wide Common SNP Models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets