Discovery, fine-mapping, and conditional analyses of genetic variants associated with C-reactive protein in multiethnic populations using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study.

C-reactive protein (CRP) is a circulating biomarker indicative of systemic inflammation. We aimed to evaluate genetic associations with CRP levels among non-European-ancestry populations through discovery, fine-mapping and conditional analyses. A total of 30 503 non-European-ancestry participants from 6 studies participating in the Population Architecture using Genomics and Epidemiology study had serum high-sensitivity CRP measurements and ∼200 000 single nucleotide polymorphisms (SNPs) genotyped on the Metabochip. We evaluated the association between each SNP and log-transformed CRP levels using multivariate linear regression, with additive genetic models adjusted for age, sex, the first four principal components of genetic ancestry, and study-specific factors. Differential linkage disequilibrium patterns between race/ethnicity groups were used to fine-map regions associated with CRP levels. Conditional analyses evaluated for multiple independent signals within genetic regions. One hundred and sixty-three unique variants in 12 loci in overall or race/ethnicity-stratified Metabochip-wide scans reached a Bonferroni-corrected P-value <2.5E-7. Three loci have no (HACL1, OLFML2B) or only limited (PLA2G6) previous associations with CRP levels. Six loci had different top hits in race/ethnicity-specific versus overall analyses. Fine-mapping refined the signal in six loci, particularly in HNF1A. Conditional analyses provided evidence for secondary signals in LEPR, IL1RN and HNF1A, and for multiple independent signals in CRP and APOE. We identified novel variants and loci associated with CRP levels, generalized known CRP associations to a multiethnic study population, refined association signals at several loci and found evidence for multiple independent signals at several well-known loci. This study demonstrates the benefit of conducting inclusive genetic association studies in large multiethnic populations.

Spatial Error Detection and Assimilation Effects in Rapid Single and Bimanual Aiming Movements.

In 2 experiments, spatial error detection capability and movement accuracy were investigated in both single and bimanual rapid aiming movements. In both experiments, right-handed college-age participants (N = 40 [Experiment 1]; N = 24 [Experiment 2]) used light, aluminum levers to make quick single and dual reversal movements in the sagittal plane in a time to reversal of 210 ms to either the same or different target locations involving identical (Experiment 1) or mirror-image (Experiment 2) movements. In Experiment 1, the shorter-distance limb overshot the target by 15-23&percent; when paired with a limb traveling at least 20 degrees farther, but no spatial assimilations were shown when movements differed by 20 degrees or less. In Experiment 2, the shorter-distance limb overshot 22-29&percent; when paired with a limb traveling 20 degrees farther, but spatial assimilations were not mitigated when both limbs moved to the same target position. Participants underestimated movement amplitude in all dual conditions but particularly when spatial assimilations were noted. Correlations between actual and estimated errors decreased from single to dual trials in both experiments. The findings suggest that spatial assimilations are caused by bimanual differences in movement amplitude, regardless of movement direction, and that individuals have greater difficulty identifying errors in simultaneous actions, especially when spatial assimilations are present, than identifying errors in single-limb actions.