Epigenetic Inheritance and the Missing Heritability Problem

Genome-wide association studies (GWASs) have successfully identified thousands of susceptibility loci for human complex diseases. However, missing heritability is still a challenging problem. Considering most GWAS loci are located in regulatory elements, we recently developed a pipeline named functional disease-associated single-nucleotide polymorphisms (SNPs) prediction (FDSP), to predict novel susceptibility loci for complex diseases based on the interpretation of regulatory features and published GWAS results with machine learning. When applied to type 2 diabetes and hypertension, the predicted susceptibility loci by FDSP were proved to be capable of explaining additional heritability. In addition, potential target genes of the predicted positive SNPs were significantly enriched in disease-related pathways. Our results suggested that taking regulatory features into consideration might be a useful way to address the missing heritability problem. We hope FDSP could offer help for the identification of novel susceptibility loci for complex diseases.

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The Human Microbiome and the Missing Heritability Problem

Frontiers in Genetics ◽

10.3389/fgene.2017.00080 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 40

Author(s):

Santiago Sandoval-Motta ◽

Maximino Aldana ◽

Esperanza Martínez-Romero ◽

Alejandro Frank

Keyword(s):

Human Microbiome ◽

Missing Heritability ◽

Missing Heritability Problem

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A Comparative Study on Multifactor Dimensionality Reduction Methods for Detecting Gene-Gene Interactions with the Survival Phenotype

BioMed Research International ◽

10.1155/2015/671859 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Seungyeoun Lee ◽

Yongkang Kim ◽

Min-Seok Kwon ◽

Taesung Park

Keyword(s):

Dimensionality Reduction ◽

Genetic Variants ◽

Multifactor Dimensionality Reduction ◽

Association Studies ◽

Gene Interactions ◽

Genome Wide Association Studies ◽

Missing Heritability ◽

Analytical Strategy ◽

Reduction Methods ◽

Missing Heritability Problem

Genome-wide association studies (GWAS) have extensively analyzed single SNP effects on a wide variety of common and complex diseases and found many genetic variants associated with diseases. However, there is still a large portion of the genetic variants left unexplained. This missing heritability problem might be due to the analytical strategy that limits analyses to only single SNPs. One of possible approaches to the missing heritability problem is to consider identifying multi-SNP effects or gene-gene interactions. The multifactor dimensionality reduction method has been widely used to detect gene-gene interactions based on the constructive induction by classifying high-dimensional genotype combinations into one-dimensional variable with two attributes of high risk and low risk for the case-control study. Many modifications of MDR have been proposed and also extended to the survival phenotype. In this study, we propose several extensions of MDR for the survival phenotype and compare the proposed extensions with earlier MDR through comprehensive simulation studies.

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A novel sibling-based design to quantify genetic and shared environmental effects: application to drug abuse, alcohol use disorder and criminal behavior

Psychological Medicine ◽

10.1017/s003329171500224x ◽

2016 ◽

Vol 46 (8) ◽

pp. 1639-1650 ◽

Cited By ~ 10

Author(s):

K. S. Kendler ◽

H. Ohlsson ◽

A. C. Edwards ◽

P. Lichtenstein ◽

K. Sundquist ◽

...

Keyword(s):

Drug Abuse ◽

Alcohol Use ◽

Environmental Effects ◽

Criminal Behavior ◽

Alcohol Use Disorder ◽

Twin Studies ◽

Missing Heritability ◽

Heritability Estimates ◽

Missing Heritability Problem ◽

Half Sibling

BackgroundTwin studies have been criticized for upwardly biased estimates that might contribute to the missing heritability problem.MethodWe identified, from the general Swedish population born 1960–1990, informative sibships containing a proband, one reared-together full- or half-sibling and a full-, step- or half-sibling with varying degrees of childhood cohabitation with the proband. Estimates of genetic, shared and individual specific environment for drug abuse (DA), alcohol use disorder (AUD) and criminal behavior (CB), assessed from medical, legal or pharmacy registries, were obtained using Mplus.ResultsAggregate estimates of additive genetic effects for DA, AUD and CB obtained separately in males and females varied from 0.46 to 0.73 and agreed with those obtained from monozygotic and dizygotic twins from the same population. Of 54 heritability estimates from individual classes of informative sibling trios (3 syndromes × 9 classes of trios × 2 sexes), heritability estimates from the siblings were lower, tied and higher than those from obtained from twins in 26, one and 27 comparisons, respectively. By contrast, of 54 shared environmental estimates, 33 were lower than those found in twins, one tied and 20 were higher.ConclusionsWith adequate information, human populations can provide many methods for estimating genetic and shared environmental effects. For the three externalizing syndromes examined, concerns that heritability estimates from twin studies are upwardly biased or were not generalizable to more typical kinds of siblings were not supported. Overestimation of heritability from twin studies is not a likely explanation for the missing heritability problem.

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Premodern Transcendental Perspectives on the Missing Heritability Problem and Some Intelligence Conundrums

Cureus ◽

10.7759/cureus.135 ◽

2013 ◽

Author(s):

Ted Christopher

Keyword(s):

Missing Heritability ◽

Missing Heritability Problem

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Dissolving the Missing Heritability Problem

Philosophy of Science ◽

10.1086/694007 ◽

2017 ◽

Vol 84 (5) ◽

pp. 1055-1067 ◽

Cited By ~ 11

Author(s):

Pierrick Bourrat ◽

Qiaoying Lu

Keyword(s):

Missing Heritability ◽

Missing Heritability Problem

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Phenotype Heritability in holobionts: An Evolutionary Model

10.1101/2020.05.05.079137 ◽

2020 ◽

Author(s):

Saúl Huitzil ◽

Santiago Sandoval-Motta ◽

Alejandro Frank ◽

Maximino Aldana

Keyword(s):

Regulatory Networks ◽

Evolutionary Model ◽

Complex Diseases ◽

Missing Heritability ◽

Phenotypic Characteristics ◽

Genetic Studies ◽

Genomic Signatures ◽

High Incidence ◽

Gene Regulatory ◽

Missing Heritability Problem

AbstractMany complex diseases are expressed with high incidence only in certain populations. Genealogy studies determine that these diseases are inherited with a high probability. However, genetic studies have been unable to identify the genomic signatures responsible for such heritability, as identifying the genetic variants that make a population prone to a given disease is not enough to explain its high occurrence within the population. This gap is known as the missing heritability problem. We know that the microbiota plays a very important role in determining many important phenotypic characteristics of its host, in particular, the complex diseases for which the missing heritability occurs. Therefore, when computing the heritability of a phenotype it is important to consider not only the genetic variation in the host but also in its microbiota. Here we test this hypothesis by studying an evolutionary model based on gene regulatory networks. Our results show that the holobiont (the host plus its microbiota) is capable of generating a much larger variability than the host alone, greatly reducing the missing heritability of the phenotype. This result strongly suggests that a considerably large part of the missing heritability can be attributed to the microbiome.

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Science's Big Problem, Reincarnation's Big Potential, and Buddhists' Profound Embarrassment

10.20944/preprints201707.0061.v1 ◽

2017 ◽

Author(s):

Ted Christopher

Keyword(s):

Deoxyribonucleic Acid ◽

Behavioral Genetics ◽

Missing Heritability ◽

Religious Perspective ◽

Individual Level ◽

Scientific Materialism ◽

Religious Perspectives ◽

The Common ◽

The Individual ◽

Missing Heritability Problem

Scientific materialism is the largely unquestioned basis for modern science's understanding of life. It also holds enormous sway beyond science and thus has increasingly marginalized religious perspectives. Yet it is easy to find behavioral phenomena from the accepted literature that seriously challenge materialism. A number of these phenomena are very suggestive of reincarnation. The larger test for science's paradigm, though, as well as for any potential general import from reincarnation - is the DNA (or genetics)-based model of heredity. If that conception-beget, DNA (deoxyribonucleic acid)-carried model can be confirmed at the individual level then in a very substantial way we would be confirmed as material-only creatures. In particular, can behavioral genetics and personal genomics confirm their DNA-based presumptions? During the last decade enormous efforts have been made to find the DNA origins for a number of health and behavioral tendencies. These efforts have been an "absolutely beyond belief" failure and it is here that the scientific vision faces its biggest challenge. The common premodern reincarnation understanding, on the other hand, fits well on a number of specific conundrums and offers a broad coherence across this unfolding missing heritability mystery. For people trying to make sense of a religious perspective or simply questioning materialism, you should be looking at the missing heritability problem.

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