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- Davies, G., et al.
(författare)
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Genetic contributions to variation in general cognitive function : a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
- 2015
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 20:2, s. 183-192
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Tidskriftsartikel (refereegranskat)abstract
- General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health-and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N = 6617) and the Health and Retirement Study (N = 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.
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| 2. |
- Lu, Yingchang, et al.
(författare)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Watson, Hunna J., et al.
(författare)
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Common Genetic Variation and Age of Onset of Anorexia Nervosa
- 2022
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Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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| 9. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 10. |
- Bjälke, Christer, et al.
(författare)
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BOF (Barnorienterad familjeterapi) : symtomens arena?
- 1999
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Barnorienterad familjeterapi - BOF, en terapiform där barn och föräldrar leker tillsammans i en sandlåda med ett material av dockor, djur, träd, staket, etc. I studien undersöker vi om man med ledning av det som sker i leken, samhandlingen, kan se och förstå barnets problem, dvs det symtom familjen sökte till BUP för.Vi valde att dela in symtomen i tre huvudgrupper; externaliserande, dvs. utagerande symtom, internaliserande symtom, dvs mer inåtvända symtom som oro, ledsenhet samt somatiserande, där symtomen tar sig kroppsliga uttryck.Nio familjer som inledde en BOF-terapi vid BUP, Vrinnevisjukhuset under 1997-98 kom att ingå i undersökningen.Innan terapin påbörjades fyllde föräldrarna i ett CBCL -formulär om barnets symtom. BOF-terapin utfördes på vanligt sätt med filmning av sessionerna och samtal i familjen om filmerna. Därefter fick vi tillgång till filmerna. Vi fick ej veta något om symtom eller problematik. I ett fall kände vi anmälningsorsaken. Familjesammansättningen var också okänd för oss.Vi har studerat den första terapiomgången med barn, föräldrar och terapeut vid sandlådan. Filmen har transkriberats vilket innebär att varje sammanhållen handling och verbal tur, dvs. yttrande, har dikterats in på band. Ex, Pojke gör: Tar bilen, Mamma säger: "Kom hit" Transkriptionen har skrivits ut och analyserats. Vi har sorterat och räknat antal handlingar och yttranden och för varje aktör. För att få veta intensiteten i leken har vi sedan delat antalet med lekens längd. Vi antog att intensivare lek kan tyda på utagerande problematik.Vi har läst materialet och försökt beskriva terapiomgångarna globalt avseende innehåll och teman i leken, gränser och aktivitet i sandlådan samt terapeutens agerande.I utskrifterna har vi även försökt finna handlingar och yttranden som visar på gränsergränssättning, aggressivitet, omsorg, oro-ängslan, sjukdom-skada, ledsenhet, att bli sedd etc. Vi har även försökt se till samspelet ur olika aspekter.De olika kategorierna har markerats i skriften, förts in i ett protokoll och räknats samman. Vi har jämfört de olika resultaten och ställt en hypotes om barnets symtom.Våra antaganden om varje barns symtom har jämförts med resultatet av CBCL-skattningen. Vi fann, att vi vid åtta av nio barn hamnat inom samma huvudgrupp av symtom som CBCL. Pojken som avvek hade, liksom flertalet av barnen, en dubbel problematik med både internaliserande och externaliserande symtom. I gruppen ingick inget barn med starka somatiserande symtom varför vi ej kan uttala oss om giltigheten för den gruppen.Vår slutsats är att barnets symtom syns i samleken och att BOF-sandlådan verkligen är symtomets arena.
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