Large-scale cis-and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression

SummaryThe inflammatory bowel diseases (IBD) are chronic gastrointestinal inflammatory disorders that affect millions worldwide. Genome-wide association studies have identified 200 IBD-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 IBD loci using high-density genotyping in 67,852 individuals. We pinpointed 18 associations to a single causal variant with >95% certainty, and an additional 27 associations to a single variant with >50% certainty. These 45 variants are significantly enriched for protein-coding changes (n=13), direct disruption of transcription factor binding sites (n=3) and tissue specific epigenetic marks (n=10), with the latter category showing enrichment in specific immune cells among associations stronger in CD and in gut mucosa among associations stronger in UC. The results of this study suggest that high-resolution fine-mapping in large samples can convert many GWAS discoveries into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.

Some researchers contend that the Rosenberg Self-Esteem Scale taps two dimensions of self-image, whereas others argue that the two dimensions (positive and negative) are merely an artifact of item wording. To directly test these competing views, we had 741 ethnically diverse university undergraduates take one of three versions of the 10-item Rosenberg Scale: the original version comprised of five positively worded and five negatively worded items, or one of two alternative versions comprised of 10 positively worded or 10 negatively worded items. Analyses indicated that the original version fit a two-factor model, whereas the reworded versions generally fit a one-factor model. All three versions had high validity for different ethnic groups, but the revised-positive version had less overlap with a measure of depression, and both revised versions had less overlap with a measure of self-deception. #

This article reports an association between the variation of dopamine D4 receptor (DRD4) allele frequencies around the globe and population migration patterns in prehistoric times. After compiling existing data on DRD4 allele frequencies of 2,320 individuals from 39 populations and on the migration pattern of these groups, we found that, compared to sedentary populations, migratory populations showed a higher proportion of long alleles for DRD4. The correlation between macro-migration (long-distance group migration) and the proportion of long alleles of DRD4 was .85 ( p Ͻ .001), and that between micro-migration (sedentary vs. nomadic settlement) and the proportion of long alleles was .52 ( p ϭ .001). We discussed the adaptive value of long alleles of DRD4-a genetic trait that has been linked in some studies to the personality trait of novelty-seeking and to hyperactivity-in migratory societies and the possibility of natural selection for a migration gene.