Population genetics and human ancestry
What is meant by ancestry?
Refers to an individual’s genetic lineage—the proportion of their genome inherited from different ancestral populations over evolutionary and historical time. It reflects patterns of shared descent and genetic similarity among groups that arose from geographic separation, migration, and admixture.
Difference between shared and non-shared environment.
Shared environmental variables are those that make individuals raised in the same family more similar to each other. Examples include socioeconomic status, parenting style, neighborhood, family values, and schooling
Non-shared (unique) environmental variables are those that make family members different from one another. These include differential peer groups, accidents or illnesses, differential treatment by parents, random life events, and measurement error.
How is haplotype related to LD?
LD reflects the preservation of ancestral haplotypes over time. When a mutation first appears, it is embedded within a particular haplotype, and nearby SNPs remain correlated with it until recombination events disrupt the pattern. Thus, haplotypes are the fundamental units that define regions of LD and enable imputation-based inference.
What is pleiotropy?
Occurs when the same genetic variant or set of variants influences multiple distinct phenotypes. In behavioral genetics, pleiotropy means that some genes contribute to risk or variation across more than one disorder or trait.
To a behavioral geneticist, what is the defining or most important difference between monozygotic and dizygotic twins?
The defining difference is genetic relatedness: monozygotic (MZ) twins share essentially 100% of their segregating genetic variance, whereas dizygotic (DZ) twins share, on average, 50%, just like ordinary siblings.
What is population stratification?
Refers to systematic differences in allele frequencies between subgroups within a population that arise from differences in ancestry rather than true causal effects on the phenotype. If not properly accounted for, these ancestry differences can create spurious associations in GWAS—that is, SNPs may appear to be related to a trait simply because both the SNP and the trait differ in frequency across ancestral groups.
What is the Wilson effect?
Refers to the well-documented finding that the heritability of intelligence (IQ) increases with age.
What is SNP imputation or tagging?
Refers to the process of predicting or inferring the genotype of unobserved single-nucleotide polymorphisms (SNPs) based on the known genotypes of nearby SNPs that are in linkage disequilibrium (LD) with them.
What is SNP heritability?
Refers to the proportion of total phenotypic variance that can be statistically attributed to the additive effects of all measured common SNPs in a GWAS. It provides an estimate of how much variance could be explained if sample size were infinite and all common SNPs contributing to the trait were detected.
What is heritability useful for?
- Estimating the proportion of phenotypic differences among individuals that are currently predictable from genetic differences.
– Predicting the response to selection (in the case of narrow-sense heritability).
– Indicating whether genetic research strategies (e.g., GWAS) are likely to be successful for a given trait.
What do geneticists know about the distribution of common genetic variants among human ancestry populations?
Common genetic variants are largely shared across all human ancestry populations. Most common variants arose before major human migrations out of Africa and therefore occur in all populations at varying frequencies. These variants tend to be globally distributed, although their allele frequencies can differ slightly due to genetic drift, migration, and local adaptation.
What are the three laws of behavior genetics?
First Law: All human behavioral traits are heritable.
Second Law: The effect of being raised in the same family is smaller than the effect of genes.
Third Law: A substantial portion of the variation in complex human traits is not accounted for by genes or the shared environment.
This residual variation reflects the influence of the non-shared environment (E), in-
cluding unique experiences and measurement error.
What is positional cloning? Is positional cloning able to tell us anything about specific genetic variants or their causes?
A method of gene identification in which researchers locate a gene associated with a particular phenotype based solely on its approximate position on a chromosome.
Positional cloning by itself cannot determine the specific causal variant or the biological mechanism underlying the association. Instead, it identifies a candidate region that likely contains one or more relevant genes.
In terms of GWAS, what do geneticists typically predict will be the relationship between effect size and allele frequency of detected hits?
In GWAS, geneticists typically expect an inverse relationship between effect size and allele frequency among detected variants. This means that common variants (high minor allele frequency) generally have small effect sizes, while rare variants (low minor allele frequency) can have larger effects.
What is heritability not usefulf for?
– Determining whether a trait is genetically fixed or immutable.
– Explaining differences between populations or across time periods.
– Interpreting heritability as applying to an individual (it is a population statistic, not an individual measure).
What are two forms of genetic drift?
1. The founder effect occurs when a small group of individuals establishes a new population that is genetically unrepresentative of the original population.
2. The bottleneck effect occurs when a population is drastically reduced in size due to a random external event. The survivors represent only a random subset of the original gene pool, leading to a loss of genetic variation and potential shifts in allele frequencies.
Both forms of drift generally decrease genetic variation within populations.
What other traits show evidence of changing variance components over time?
Traits like political and social attitudes, values, and certain behavioral problems (e.g., antisocial behavior, substance use) show stronger shared environmental effects in adolescence that fade by adulthood, paralleling the developmental pattern seen for IQ.
What is meant by allelic association? In allelic association, what statistical metric is most commonly used to represent risk?
Refers to a population-level relationship between a specific allele at a genetic locus and a phenotype or disease. It occurs when certain alleles are found more (or less) frequently among individuals with a trait or disorder than among those without it.
The statistical metric most commonly used to represent risk in allelic association studies is the odds ratio (OR).
Between increasing GWAS sample sizes, SNP heritability estimates, and inclusion of rare variants, is it feasible to account for most of the so-called missing heritability?
Yes.
Biometric components of parent-offspring, full siblings, or half-siblings?
Parent–offspring pairs: share 50% of additive genetic variance (A), 0% of dominance or epistatic effects (since only one allele is transmitted from each parent), and do not perfectly share environment (C only if reared together).
– Full siblings: same expectations as DZ twins – 50% of A, 25% of D, 0% of I, and shared C.
– Half-siblings: share 25% of additive genetic variance (A) on average, 0% of dominance or epistasis, and may or may not share the same environment depending on upbringing.
Methods used to address population stratification?
1. Including ancestry covariates in GWAS analyses to statistically control for subtle population structure.
2. Using mixed models or linear mixed effects models that account for relatedness and population structure directly through a genomic relationship matrix.
3. Restricting analyses to relatively homogeneous ancestry groups to reduce confounding, though this limits generalizability.
4. Applying within-family designs, which automatically control for ancestry because family members share the same ancestral background.
What seems to be the impact of being reared together or apart on the correlation between the personality scores of relatives?
Being reared together or apart has surprisingly little effect on the correlation between relatives’ personality scores. Studies show that monozygotic (MZ) twins reared apart are about as similar in personality as MZ twins reared together, indicating that shared rearing environment contributes very little to adult personality resemblance.
In the Sanders et al. (2008) candidate gene study of schizophrenia, they found 30 genetic variants significant at p < .05 and 3 variants significant at p < .01. Given the total number of independent tests the authors conducted, do these variants actually reach genome-wide significance? Why or why not?
No. Even though Sanders et al. (2008) reported several nominal associations, genome–wide significance requires correcting for the total number of independent tests. In short, given the large testing burden, the reported variants do not reach genome–wide significance because their p–values are not small enough after accounting for multiple comparisons, making them likely false positives absent independent replication.
How does pleiotropy relate to genetic correlations?
For multifactorial psychiatric phenotypes such as schizophrenia, bipolar disorder, and major depression, researchers find substantial positive genetic correlations. These findings indicate broad pleiotropy among psychiatric disorders and suggest that current diagnostic categories only partially reflect the underlying causal architecture.
What is the representative assumption of twin designs?
Twins are representative of the general (singleton) population for the traits under study. If twins differ systematically from non-twins, results might not generalize.
Evidence: Numerous studies indicate that twins are broadly comparable to singletons on most psychological and behavioral measures, suggesting that this assumption does not seriously threaten the validity of twin study findings.