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- Witt, S. H., et al.
(författare)
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Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia
- 2017
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P = 4.42 x 10(-7)) and PKP4 (P = 8.67 x 10(-7)); and gene-set analysis yielded a significant finding for exocytosis (GO: 0006887, PFDR = 0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (r(g) = 0.28 [P = 2.99 x 10(-3)]), SCZ (r(g) = 0.34 [P = 4.37 x 10(-5)]) and MDD (r(g) = 0.57 [P = 1.04 x 10(-3)]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.
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- Watson, H. J., et al.
(författare)
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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:8, s. 1207-
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Tidskriftsartikel (refereegranskat)abstract
- Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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- Charney, A. W., et al.
(författare)
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Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder
- 2017
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P = 3.28 x 10(-8)) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h(2) = 0.35; BD II SNP-h(2) = 0.25; P = 0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.
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- Nilsson, I. A. K., et al.
(författare)
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Plasma neurofilament light chain concentration is increased in anorexia nervosa
- 2019
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality and, to a large extent, unknown pathophysiology. Structural brain differences, such as global or focal reductions in grey or white matter volumes, as well as enlargement of the sulci and the ventricles, have repeatedly been observed in individuals with AN. However, many of the documented aberrances normalize with weight recovery, even though some studies show enduring changes. To further explore whether AN is associated with neuronal damage, we analysed the levels of neurofilament light chain (NfL), a marker reflecting ongoing neuronal injury, in plasma samples from females with AN, females recovered from AN (AN-REC) and normal-weight age-matched female controls (CTRLS). We detected significantly increased plasma levels of NfL in AN vs CTRLS (median(AN) = 15.6 pg/ml, IQR(AN) = 12.1-21.3, median(CTRL) = 9.3 pg/ml, IQR(CTRL) = 6.4-12.9, and p < 0.0001), AN vs AN-REC (median(AN-REC) = 11.1 pg/ml, IQR(AN-REC) = 8.6-15.5, and p < 0.0001), and AN-REC vs CTRLS (p = 0.004). The plasma levels of NfL are negatively associated with BMI overall samples (beta (+/- se) = -0.62 +/- 0.087 and p = 6.9. 10(-12)). This indicates that AN is associated with neuronal damage that partially normalizes with weight recovery. Further studies are needed to determine which brain areas are affected, and potential long-term sequelae.
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