| 1. |
- Law, Philip J., et al.
(författare)
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Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- B-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22.2 (NCK1, rs11715604, P = 1.60 × 10-9) with opposing effects between CLL (P = 1.97 × 10-8) and HL (P = 3.31 × 10-3). Eight established non-HLA risk loci showed pleiotropic associations. Within the HLA region, Ser37 + Phe37 in HLA-DRB1 (P = 1.84 × 10-12) was associated with increased CLL and HL risk (P = 4.68 × 10-12), and reduced MM risk (P = 1.12 × 10-2), and Gly70 in HLA-DQB1 (P = 3.15 × 10-10) showed opposing effects between CLL (P = 3.52 × 10-3) and HL (P = 3.41 × 10-9). By integrating eQTL, Hi-C and ChIP-seq data, we show that the pleiotropic risk loci are enriched for B-cell regulatory elements, as well as an over-representation of binding of key B-cell transcription factors. These data identify shared biological pathways influencing the development of CLL, HL and MM. The identification of these risk loci furthers our understanding of the aetiological basis of BCMs.
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| 2. |
- Liu, Can, et al.
(författare)
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Interpregnancy Interval and Subsequent Severe Maternal Morbidity : A 16-Year Population-Based Study From California
- 2021
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 190:6, s. 1034-1046
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Tidskriftsartikel (refereegranskat)abstract
- Interpregnancy interval (IPI) is associated with adverse perinatal outcomes, but its contribution to severe maternal morbidity (SMM) remains unclear. We examined the association between IPI and SMM, using data linked across sequential pregnancies to women in California during 1997-2012. Adjusting for confounders measured in the index pregnancy (i.e., the first in a pair of consecutive pregnancies), we estimated adjusted risk ratios for SMM related to the subsequent pregnancy. We further conducted within-mother comparisons and analyses stratified by parity and maternal age at the index pregnancy. Compared with an IPI of 18-23 months, an IPI of <6 months had the same risk for SMM in between-mother comparisons (adjusted risk ratio (aRR) = 0.96, 95% confidence interval (CD: 0.91, 1.02) but lower risk in within-mother comparisons (aRR = 0.76, 95 degrees/0 CI: 0.67, 0.86). IPIs of 24-59 months and >= 60 months were associated with increased risk of SMM in both between-mother (aRR = 1.18 (95% CI: 1.13, 1.23) and aRR = 1.76 (95% CI: 1.68, 1.85), respectively) and within-mother (aRR = 1.22 (95% CI: 1.11, 1.34) and aRR = 1.88 (95% CI: 1.66, 2.13), respectively) comparisons. The association between IPI and SMM did not vary substantially by maternal age or parity. In this study, longer IPI was associated with increased risk of SMM, which may be partly attributed to interpregnancy health.
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| 3. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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