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- Ilinca, A., et al.
(författare)
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Whole-Exome Sequencing in 22 Young Ischemic Stroke Patients With Familial Clustering of Stroke
- 2020
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 51:4, s. 1056-1063
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Tidskriftsartikel (refereegranskat)abstract
- Backgrounds and Purpose-Although new methods for genetic analyses are rapidly evolving, there are currently knowledge gaps in how to detect Mendelian forms of stroke. Methods-We performed whole-exome sequencing in 22 probands, under 56 years at their first ischemic stroke episode, from multi-incident stroke families. With the use of a comprehensive stroke-gene panel, we searched for variants in stroke-related genes. The probands' clinical stroke subtype was related to clinical characteristics previously associated with pathogenic variants in these genes. Relatives were genotyped in 7 families to evaluate stroke-gene variants of unknown significance. In 2 larger families with embolic stroke of unknown source, whole-exome sequencing was performed in additional members to examine the possibility of identifying new stroke genes. Results-Six of 22 probands carried pathogenic or possibly pathogenic variants in genes reported to be associated with their stroke subtype. A known pathogenic variant in NOTCH3 and a possibly pathogenic variant in ACAD9 gene were identified. A novel JAK2:c.3188G>A (p.Arg1063His) mutation was seen in a proband with embolic stroke of undetermined source and prothrombotic status. However, penetrance in the family was incomplete. COL4A2:c.3368A>G (p.Glu1123Gly) was detected in 2 probands but did not cosegregate with the disease in their families. Whole-exome sequencing in multiple members of 2 pedigrees with embolic stroke of undetermined source revealed possibly pathogenic variants in genes not previously associated with stroke, GPR142:c.148C>G (p.Leu50Val), and PTPRN2:c.2416A>G (p.Ile806Val); LRRC1 c.808A>G (p.Ile270Val), SLC7A10c.1294dupG (p.Val432fs), IKBKB: c.1070C>T (p.Ala357Val), and OXGR1 c.392G>A (p.Arg131His), respectively. Conclusions-Screening with whole-exome sequencing using a comprehensive stroke-gene panel may identify rare monogenic forms of stroke, but careful evaluation of clinical characteristics and potential pathogenicity of novel variants remain important. In our study, the majority of individuals with familial aggregation of stroke lacked any identified genetic causes.
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| 2. |
- Phillips, S. P., et al.
(författare)
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Systematic review of methods used to study the intersecting impact of sex and social locations on health outcomes
- 2020
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Ingår i: SSM - Population Health. - : Elsevier BV. - 2352-8273. ; 12
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Forskningsöversikt (refereegranskat)abstract
- Purpose: Independent health impacts of sex or social circumstances are well-studied, particularly among older adults. Less theorized or examined is how combinations or intersections of these underpin differential health effects. Nevertheless, and often without naming it as such, an intersectional framework aligns with studies of social determinants of health, life-course epidemiology and eco-epidemiology. In this systematic review we examined and aimed to identify research methods used to operationalize, whether intentionally or inadvertently, interconnected effects of sex and social locations on health outcomes for 45+ year olds.Methods: Using broad search terms, numerous databases, and following Prisma guidelines, 732 of 9214 papers initially identified, met inclusion criteria for full review.Results: Of the 501 papers included after full review, methods used in considering intersections of sex and social circumstances/location(s) included regression (112 of 365 papers), growth curves (7 of 22), multilevel (15 of 25), decomposition (6 of 9), mediation (10 of 17), structural equation modelling (23 of 25), and other (2 of 3). Most (n = 157) approximated intersectional analyses by including interaction terms or sex-stratifying results.Discussion: Few authors used the inherent strength of some study methods to examine intersecting traits. As even fewer began with an intersectionality framework their subsequent failure to deliver cannot be faulted, despite many studies including data and methodologies that would support intersectional analyses. There appeared to be a gap, not in analytic potential but rather in theorizing that differential distributions of social locations describe heterogeneity within the categories 'men' and 'women' that can underlie differential, gendered effects on older adults' health. While SEM, mediation and decomposition analyses emerged as particularly robust methods, the unexpected outcome was finding how few researchers consider intersectionality as a potential predictor of health.
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