SummaryMany common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.

Background C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We aimed to identify genetic variants that are associated with CRP levels. Methods and Results We performed a genome wide association (GWA) analysis of CRP in 66,185 participants from 15 population-based studies. We sought replication for the genome wide significant and suggestive loci in a replication panel comprising 16,540 individuals from ten independent studies. We found 18 genome-wide significant loci and we provided evidence of replication for eight of them. Our results confirm seven previously known loci and introduce 11 novel loci that are implicated in pathways related to the metabolic syndrome (APOC1, HNF1A, LEPR, GCKR, HNF4A, and PTPN2), immune system (CRP, IL6R, NLRP3, IL1F10, and IRF1), or that reside in regions previously not known to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4, ASCL1, RORA, and BCL7B). We found significant interaction of body mass index (BMI) with LEPR (p<2.9×10−6). A weighted genetic risk score that was developed to summarize the effect of risk alleles was strongly associated with CRP levels and explained approximately 5% of the trait variance; however, there was no evidence for these genetic variants explaining the association of CRP with coronary heart disease. Conclusion We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation.

PurposeTo report the ocular characteristics and the presence of viral RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens in a patient with confirmed 2019 novel coronavirus disease (COVID-19).Participant and methodsA 30-year-old man with confirmed COVID-19 and bilateral acute conjunctivitis which occurred 13 days after illness onset. Based on detailed ophthalmic examination, reverse transcription PCR (RT-PCR) was performed to detect SARS-CoV-2 virus in conjunctival swabs. The ocular characteristics, presence of viral RNA and viral dynamics of SARS-CoV-2 in the conjunctival specimens were evaluated.ResultsSlit lamp examination showed bilateral acute follicular conjunctivitis. RT-PCR assay demonstrated the presence of viral RNA in conjunctival specimen 13 days after onset (cycle threshold value: 31). The conjunctival swab specimens remained positive for SARS-CoV-2 on 14 and 17 days after onset. On day 19, RT-PCR result was negative for SARS-CoV-2.ConclusionSARS-CoV-2 is capable of causing ocular complications such as viral conjunctivitis in the middle phase of illness. Precautionary measures are recommended when examining infected patients throughout the clinical course of the infection. However, conjunctival sampling might not be useful for early diagnosis because the virus may not appear initially in the conjunctiva.

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.