Interpreting SNP heritability in admixed populations.

Single-nucleotide polymorphism (SNP) heritability (hsnp2) is defined as the proportion of phenotypic variance explained by genotyped SNPs and is believed to be a lower bound of heritability (h2), being equal to it if all causal variants are genotyped. Despite the simple intuition behind hsnp2, its interpretation and equivalence to h2 is unclear, particularly in the presence of admixture and assortative mating. Here, we use analytical theory and simulations to describe the behavior of h2 and three widely used random-effect estimators of hsnp2-genome-wide restricted maximum likelihood, Haseman-Elston regression, and LD score regression-in admixed populations.

The multi-scale complexity of human genetic variation beyond continental groups.

Traditional clustering and visualization approaches in human genetics often operate under frameworks that assume inherent, discrete groupings. These methods can inadvertently simplify multifaceted relationships, functioning to entrench the idea of typological groups. We introduce a network-based pipeline and visualization tool grounded in relational thinking, which constructs networks from a variety of genetic similarity metrics.

Interpreting SNP heritability in admixed populations.

SNP heritability is defined as the proportion of phenotypic variance explained by genotyped SNPs and is believed to be a lower bound of heritability , being equal to it if all causal variants are genotyped. Despite the simple intuition behind , its interpretation and equivalence to is unclear, particularly in the presence of admixture and assortative mating. Here we use analytical theory and simulations to describe the behavior of and three widely used random-effect estimators of - Genome-wide restricted maximum likelihood (GREML), Haseman-Elston (HE) regression, and LD score regression (LDSC) - in admixed populations.

The genetic and phenotypic correlates of mtDNA copy number in a multi-ancestry cohort.

Mitochondrial DNA copy number (mtCN) is often treated as a proxy for mitochondrial (dys-) function and disease risk. Pathological changes in mtCN are common symptoms of rare mitochondrial disorders, but reported associations between mtCN and common diseases vary across studies. To understand the biology of mtCN, we carried out genome- and phenome-wide association studies of mtCN in 30,666 individuals from the Penn Medicine BioBank (PMBB)-a diverse cohort of largely African and European ancestry.

High-throughput phenotyping methods for quantifying hair fiber morphology.

Quantifying the continuous variation in human scalp hair morphology is of interest to anthropologists, geneticists, dermatologists and forensic scientists, but existing methods for studying hair form are time-consuming and not widely used. Here, we present a high-throughput sample preparation protocol for the imaging of both longitudinal (curvature) and cross-sectional scalp hair morphology. Additionally, we describe and validate a new Python package designed to process longitudinal and cross-sectional hair images, segment them, and provide measurements of interest.

Demographic history mediates the effect of stratification on polygenic scores.

Population stratification continues to bias the results of genome-wide association studies (GWAS). When these results are used to construct polygenic scores, even subtle biases can cumulatively lead to large errors. To study the effect of residual stratification, we simulated GWAS under realistic models of demographic history.

Bottleneck and selection in the germline and maternal age influence transmission of mitochondrial DNA in human pedigrees.

Heteroplasmy-the presence of multiple mitochondrial DNA (mtDNA) haplotypes in an individual-can lead to numerous mitochondrial diseases. The presentation of such diseases depends on the frequency of the heteroplasmic variant in tissues, which, in turn, depends on the dynamics of mtDNA transmissions during germline and somatic development. Thus, understanding and predicting these dynamics between generations and within individuals is medically relevant.

MeshMonk: Open-source large-scale intensive 3D phenotyping.

Dense surface registration, commonly used in computer science, could aid the biological sciences in accurate and comprehensive quantification of biological phenotypes. However, few toolboxes exist that are openly available, non-expert friendly, and validated in a way relevant to biologists. Here, we report a customizable toolbox for reproducible high-throughput dense phenotyping of 3D images, specifically geared towards biological use.

Facial masculinity does not appear to be a condition-dependent male ornament and does not reflect MHC heterozygosity in humans.

Recent studies have called into question the idea that facial masculinity is a condition-dependent male ornament that indicates immunocompetence in humans. We add to this growing body of research by calculating an objective measure of facial masculinity/femininity using 3D images in a large sample ( = 1,233) of people of European ancestry. We show that facial masculinity is positively correlated with adult height in both males and females.

Investigating mitonuclear interactions in human admixed populations.

To function properly, mitochondria utilize products of 37 mitochondrial and >1,000 nuclear genes, which should be compatible with each other. Discordance between mitochondrial and nuclear genetic ancestry could contribute to phenotypic variation in admixed populations. Here, we explored potential mitonuclear incompatibility in six admixed human populations from the Americas: African Americans, African Caribbeans, Colombians, Mexicans, Peruvians and Puerto Ricans.

Measuring asymmetry from high-density 3D surface scans: An application to human faces.

Perfect bilateral symmetry is the optimal outcome of the development of bilateral traits in the absence of developmental perturbations. Any random perturbation in this perfect symmetrical state is called Fluctuating Asymmetry (FA). Many studies have been conducted on FA as an indicator of Developmental Instability (DI) and its possible link with stress and individual quality in general and with attractiveness, health and level of masculinity or femininity in humans.

High Levels of Copy Number Variation of Ampliconic Genes across Major Human Y Haplogroups.

Because of its highly repetitive nature, the human male-specific Y chromosome remains understudied. It is important to investigate variation on the Y chromosome to understand its evolution and contribution to phenotypic variation, including infertility. Approximately 20% of the human Y chromosome consists of ampliconic regions which include nine multi-copy gene families.

Correction: Investigating the case of human nose shape and climate adaptation.

[This corrects the article DOI: 10.1371/journal.pgen.

Investigating the case of human nose shape and climate adaptation.

The evolutionary reasons for variation in nose shape across human populations have been subject to continuing debate. An import function of the nose and nasal cavity is to condition inspired air before it reaches the lower respiratory tract. For this reason, it is thought the observed differences in nose shape among populations are not simply the result of genetic drift, but may be adaptations to climate.

The conditioning of intervention effects on early adolescent alcohol use by maternal involvement and dopamine receptor D4 (DRD4) and serotonin transporter linked polymorphic region (5-HTTLPR) genetic variants.

Data drawn from the in-home subsample of the PROSPER intervention dissemination trial were used to investigate the moderation of intervention effects on underage alcohol use by maternal involvement and candidate genes. The primary gene examined was dopamine receptor D4 (DRD4). Variation in this gene and maternal involvement were hypothesized to moderate the influence of intervention status on alcohol use.

Modeling 3D facial shape from DNA.

Human facial diversity is substantial, complex, and largely scientifically unexplained. We used spatially dense quasi-landmarks to measure face shape in population samples with mixed West African and European ancestry from three locations (United States, Brazil, and Cape Verde). Using bootstrapped response-based imputation modeling (BRIM), we uncover the relationships between facial variation and the effects of sex, genomic ancestry, and a subset of craniofacial candidate genes.