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- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 5. |
- Elwing, B, et al.
(författare)
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A comparative study of food intake between Lithuanian and Swedish middle-aged men : The LiVicordia study
- 2001
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Ingår i: Scandinavian Journal of Nutrition/Næringsforskning. - 1102-6480 .- 1651-2359. ; 45:3, s. 126-130
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Background: In 1994, the mortality in coronary heart disease was four times higher among Lithuanian middle-aged men than among Swedish men. Over the period 1993-1995, the LiVicordia study investigated possible causes for this difference. We have earlier reported lower serum levels of cholesterol and higher susceptibility of low-density lipoprotein cholesterol for oxidation among Lithuanian men. Objective: In this part of the study, the aim was to compare mean estimates of food intake. Design: Cross-sectional study of random samples of 50-year-old men from each of the cities of Link÷ping, Sweden and Vilnius, Lithuania (n=150). The volunteers were interviewed about their food intake with the 24-hour recall method. Results: We found no differences in total energy intake, but Vilnius men had a higher energy intake from fat. Vilnius men consumed more fat from meat and less vegetable fat, while fat intake from dairy products was almost the same. Also, Vilnius men had a higher intake of vegetables, while Link÷ping men had a higher intake of fruit and berries. Conclusion: The observed differences in food consumption and dietary composition are partly consistent with the higher CHD mortality among Lithuanian men. However, data on biomarkers indicate that other dietary and lifestyle factors play a role.
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| 9. |
- Zieden, B, et al.
(författare)
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Long chain polyunsaturated fatty acids may account for higher low-density lipoprotein oxidation susceptibility in Lithuanian compared to Swedish men
- 2002
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 62:4, s. 307-314
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Mortality in coronary heart disease among middle-aged men is four times higher in Lithuania than in Sweden. Traditional risk factors cannot account for this difference. We earlier reported that low-density lipoprotein (LDL) in Lithuanian men showed a lower resistance to oxidation, measured as LDL lag time during copper oxidation, than that in Swedish men. Serum concentrations of several fat-soluble antioxidant vitamins were lower among Lithuanian men. The aim of this study was to investigate whether differences in LDL fatty acid composition could account for the difference in LDL oxidation susceptibility between men in the two countries. Methods: This cross-sectional study included randomly selected healthy 50-year-old men from Vilnius, Lithuania (n = 50) and Link÷ping, Sweden (n = 50). Main outcome measures were fatty acids in LDL, phospholipid (PL) and cholesterol ester (CE) fractions of LDL and LDL oxidation susceptibility. Results: The mean proportions of PL 20:5n3 (eicosapentaenoic acid, EPA) were higher in Vilnius men (2.09▒1.05 vs. 1.53▒0.58%, p = 0.004). LDL lag time was shorter in Vilnius men, mean▒SD (75.4▒13.6 vs. 89.5▒13.1 mins, p<0.0001) than in Link÷ping men. Mean serum ?-tocopherol was lower in Vilnius men (0.07▒0.05 vs. 0.12▒0.04 ╡g/mmol, p<0.0001) but a-tocopherol did not differ. In a multiple regression analysis controlled for city, high PL-EPA, low a-tocopherol, and high plasma triglycerides significantly contributed to a short LDL lag time, r2 = 0.53. Conclusions: Fat quality, i.e. poly unsaturated fatty acids especially LDL-EPA, plasma triglycerides and antioxidative vitamins may partly account for the increased LDL oxidation susceptibility found in Vilnius men compared with Link÷ping men.
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