Multiethnic Meta-Analysis Identifies Ancestry-Specific and Cross-Ancestry Loci for Pulmonary Function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of l

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci

Prosocial effect.

<p>Donors’ (n = 31) pulling of the prosocial distribution ([0,1], or [1,1], respectively) in the presence (test condition, dark bar) or absence (control condition, light bar) of a recipient, for both versions of the dictator game. A prosocial effect was present only in the costly version of the game. ***: p<0.001.</p

Rasch analyses.

<p>The higher the “item difficulty” - score, the higher the difficulty level of the item. Fit statistics (standardized infit and outfit values) have an expected value of 0. Values >2.0 indicate a misfit <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068440#pone.0068440-Wright1" target="_blank">[77]</a>.</p

Effect of signs and signals of need on prosocial pulling.

<p>Percentage of trials in which prosocial pulling occurred following different kinds of signaling (dark bars) or without signaling (light bars). Figures inside the bars represent numbers of trials. For instance, prosocial pulling occurred in 85% of 121 trials in which no signaling of any kind occurred (total). Looking = recipient looks at reward; reaching = recipient tries to access reward with arm, request = recipient verbally asks for reward.</p

Attention of donors to the partner’s plate before pulling.

<p>Percentage of trials when donors looked at the partner’s plate in test sessions of the costly version (reward on partner’s side), the cost-free version (reward on both sides) and during motivation trials (one reward on donor’s side). The presence of a reward for the partner in addition to a reward to the subject herself does not increase attention to the partner’s plate.</p