Dong Li,Xiao Chang,John J. Connolly,Lifeng Tian,Yichuan Liu,Elizabeth J. Bhoj,Nora Robinson,Debra Abrams,Yun R. Li,Jonathan P. Bradfield,Cecilia E. Kim,Jin Li,Fengxiang Wang,James Snyder,Maria Lemma,Cuiping Hou,Zhi Wei,Yiran Guo,Haijun Qiu,Frank D. Mentch,Kelly A. Thomas,Rosetta M. Chiavacci,Roger Cone,Bingshan Li,Patrick A. Sleiman,Hakon Hakonarson,Ted Reichborn-Kjennerud,Gun Peggy Knudsen,Ole Andreas Andreassen,Thomas Espeseth,Laura M Huckins,Ivar Reinvang,Vidar Martin Steen,Stephanie Le Hellard,Morten Mattingsdal,Federica Tozzi,Kirsty Kiezebrink,Johannes Hebebrand,Philip Gorwood,Roger A H Adan,Martien J H Kas,Angela Favaro,Paolo Santonastaso,Fernando Fernande-Aranda,Monica Gratacos,Filip Rybakowski,Monika Dmitrzak-Weglarz,Jaakko Kaprio,Anna Keski-Rahkonen,Anu Raevuori-Helkamaa,Eric F Van Furth,Margarita C T Slof-Opt Landt,James I Hudson,Ted Reichborn-Kjennerud,Gun Peggy S Knudsen,Palmiero Monteleone,Andreas Karwautz,Wade H Berrettini,Nicholas J Schork,Tetsuya Ando,Hidetoshi Inoko,Tonu Esko,Krista Fischer,Katrin Mannik,Andres Metspalu,Jessica H Baker,Janiece E DeSocio,Christopher E Hilliard,Julie K O'Toole,Jacques Pantel,Jin P Szatkiewicz,Stephanie Zerwas,Oliver S P Davis,Sietske Helder,Katharina Buhren,Roland Burghardt,Martina De Zwaan,Karin Egberts,Stefan Ehrlich,Beate Herpertz-Dahlmann,Wolfgang Herzog,Hartmut Imgart,Andre Scherag,Stephan Zipfel,Claudette Boni,Nicolas Ramoz,Audrey Versini,Unna N Danner,Judith Hendriks,Bobby P C Koeleman,Roel A Ophoff,Eric Strengman,Annemarie A Van Elburg,Alice Bruson,Maurizio Clementi,Daniela Degortes,Monica Forzan,Elena Tenconi,Elisa Docampo,Georgia Escaramis,Susana Jimenez-Murcia,Jolanta Lissowska,Andrzej Rajewski,Neonila Szeszenia-Dabrowska,Agnieszka Slopien,Joanna Hauser,Leila Karhunen,Ingrid Meulenbelt,P Eline Slagboom,Alfonso Tortorella,Mario Maj,George Dedoussis,DImitris DIkeos,Fragiskos Gonidakis,Konstantinos Tziouvas,Artemis Tsitsika,Hana Papezova,Lenka Slachtova,Debora Martaskova,James L Kennedy,Robert D Levitan,Zeynep Yilmaz,Julia Huemer,Doris Koubek,Elisabeth Merl,Gudrun Wagner,Paul Lichtenstein,Gerome Breen,Sarah Cohen-Woods,Anne Farmer,Peter McGuffin,Sven Cichon,Ina Giegling,Stefan Herms,Dan Rujescu,Stefan Schreiber,H-Erich Wichmann,Christian DIna,Rob Sladek,Giovanni Gambaro,Nicole Soranzo,Antonio Julia,Sara Marsal,Raquel Rabionet,Valerie Gaborieau,Danielle M DIck,Aarno Palotie,Samuli Ripatti,Elisabeth Widen,Ole A Andreassen,Thomas Espeseth,Astri Lundervold,Ivar Reinvang,Vidar M Steen,Stephanie Le Hellard,Morten Mattingsdal,Ioanna Ntalla,Vladimir Bencko,Lenka Foretova,Vladimir Janout,Marie Navratilova,Steven Gallinger,Dalila Pinto,Stephen W Scherer,Harald Aschauer,Laura Carlberg,Alexandra Schosser,Lars Alfredsson,Bo DIng,Lars Klareskog,Leonid Padyukov,Chris Finan,Gursharan Kalsi,Marion Roberts,Jeff C Barrett,Xavier Estivill,Anke Hinney,Patrick F Sullivan,Eleftheria Zeggini,Cynthia M Bulik,Harry Brandt,Steve Crawford,Scott Crow,Manfred M Fichter,Katherine A Halmi,Craig Johnson,Allan S Kaplan,Maria C La Via,James Mitchell,Michael Strober,Alessandro Rotondo,Janet Treasure,D Blake Woodside,Pamela K Keel,Kelly L Klump,Lisa Lilenfeld,Andrew W Bergen,Walter Kaye,Pierre Magistretti,
(2017). A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling. Scientific Reports. ISSN 2045-2322. 7:3847s 1-9. doi: 10.1038/s41598-017-01674-8.
Ted Reichborn-Kjennerud,Gun Peggy Knudsen,Ole Andreas Andreassen,Thomas Espeseth,Astri Lundervold,Ivar Reinvang,Vidar Martin Steen,Stephanie Le Hellard,Morten Mattingsdal,V Boraske,CS Franklin,James A. B. Floyd,Laura M Thornton,L. M. Huckins,L Southam,NW Rayner,I Tachmazidou,KL Klump,Jim Treasure,C. M. Lewis,U Schmidt,F Tozzi,K Kiezebrink,J. Hebebrand,P. Gorwood,R. A. H. Adan,M. J. H. Kas,A Favaro,P Santonastaso,Fernando Fernández-Aranda,Mònica Gratacòs,Finn Rybakowski,M. Dmitrzak-Weglarz,J Kaprio,A Keski-Rahkonen,A. Raevuori,E. F. Van Furth,M. C. T. Slof-Op 't Landt,JI Hudson,P. Monteleone,AS Kaplan,A Karwautz,H Hakonarson,W. H. Berrettini,Y Guo,D Li,NJ Schork,G Komaki,T Ando,H. Inoko,
(2014). A genome-wide association study of anorexia nervosa. Molecular Psychiatry. ISSN 1359-4184. 19(10), s 1085-1094. doi: 10.1038/mp.2013.187.
Backgroundand Aims: The stability over time for avoidant personality disorder (AVPD) and obsessive-compulsive personality disorder (OCPD) has previously been found to be moderate. However, the mechanisms underlying this temporal development are not well understood. In the present study we estimate the influence of genetic and environmental factors on stability and change in AVPD and OCPD. Methods: AVPD and OCPD traits were assessed using the Structured Interview for DSM-IV Personality in 2,793 young adult twins from the Norwegian Institute of Public Health Twin Panel (wave 1). On average 10 years later (wave 2) 2,282 of these were re-interviewed. Longitudinal biometric models were fitted to dimensional representations of AVPD and OCPD. Results: The number of endorsed sub-threshold criteria for both PDs decreased 31% from wave 1 to wave 2. The correlations between the numbers of traits endorsed at the two time points were 0.54 for AVPD and 0.37 for OCPD. Genetic factors contributed 67% and 53%, respectively, to the stability of AVPD and OCPD. The correlations between the genetic factors influencing AVPD and OCPD at the two time points were 1.00 and 0.72 respectively, while the environmental influences correlated 0.26 and 0.23, respectively. The correlation between the stable risk factors for AVPD and OCPD was 0.39 of which 63% was attributable to genetic influences. Conclusion: Both AVPD and OCPD were moderately stable from young to middle adulthood. Stability was in large part due to genetic factors, whereas environmental influences contributed to change.
Background and Aims: Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood. Methods: DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2,282 Norwegian twins in early adulthood and approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria. Results: The mean criterion count for ASPD and BPD decreased 40% and 28% respectively from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15 respectively for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43 respectively at both time points. Conclusion: ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the10 year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD.
Background and aims: Substantial correlations between normal and abnormal personality traits have been found, but there is still little knowledge regarding the extent to which the underlying genetic and environmental influences are shared. Methods: 2,282 Norwegian twins were assessed for DSM-IV criteria for personality disorders using structured interviews. Ten years later years the twins were re-interviewed, and normal personality was assessed using the Big Five Inventory. Multivariate twin models were fitted to the five domains of normal personality and dimensional measures of each of the personality disorders individually. Results: While the heritability of the number endorsed criteria for the personality disorders ranged from 0.2 to 0.41, the proportion of genetic variance that was unique to each PD ranged from 19% for Avoidant to 79% for Schizotypal, with a median of 58% across all PDs. Conversely, the proportion of environmental variance unique to the personality disorder criteria ranged from 79% to 99%, with median of 97%. Conclusion: Our results suggest that a considerable proportion of the genetic variance and virtually all environmental variance is unique to the personality disorders, and not shared with the five broad domains of normal personality.
A possible new immunodeficiency syndrome was reported in 1978. The male patient had a transient block in the normal maturation of B cells and intractable diarrhoea, and died at age 8 months. Three diseased brothers probably had the same disorder. Their two sisters have since had two and one affected sons respectively. All seven affected boys were dystrophic at birth. They were stillborn or died in early infancy, except one boy who died at age 5 years. This boy developed signs of hypohidrotic ectodermal dysplasia, with thin hair, small cone-shaped teeth and oligodontia, but with no periorbital wrinkling. At age 8 months he started having serious pneumococcal infections which were difficult to treat. He also developed an inflammatory bowel disease. All three obligate female carriers had small teeth and reported lack of sweating. One carrier had a highly skewed X-inactivation, whereas two carriers had a random X inactivation. Haplotype analysis showed that both affected and unaffected family members shared markers flanking the hypohidrotic ectodermal dysplasia (ED1) gene. Affected members shared markers in the regions Xp21.1-p11.4 and Xq27-qtel. A novel X-linked disorder of immunodeficiency and hypohidrotic ectodermal dysplasia has been reported. This disorder is allelic to incontinentia pigmenti, and the patients had mutations in exon 10 of the IKK-gamma (NEMO) gene. The findings in our family bear some similarity to this novel immunodeficiency. However, no mutations in exon 10 were found. Our family may represent a mutation in other parts of the NEMO gene or yet another X-linked immunodeficiency syndrome.
Elderly females have a higher frequency of skewed X-inactivation in peripheral blood cells. G6PD-linked genes have been implicated in this age-related skewing of X-inactivation in Safari cats. In a study of X inactivation in 71 elderly monozygotic twin pairs, we found a strong tendency for the same cell line of blood cells to be the predominant cell line in twin pairs. In the present work we tested the possibility that age-related skewing of X-inactivation is related to a locus linked to the G6PD gene in humans. We analyzed X inactivation in 101 dizygotic twin pairs aged 73-93 years. The X inactivation pattern was classified as skewed when 80% or more of the cells had the same X-chromosome active. The frequency of skewed X inactivation in the twins (37%) was highly increased compared to blood donors aged 19-65 years (7%). The correlation coefficient for the X inactivation pattern was 0.23 (P=0.02) for the dizygotic twin pairs and 0.52 (P<0.01) for the monozygotic twin pairs, confirming a genetic influence on X inactivation phenotype in elderly females. Analysis of markers in the G6PD region (F8C and DXS15) showed a significant tendency for twins who had inherited different maternal alleles in these markers to be discordant for X inactivation phenotype (one twin having a skewed and the other twin having a non-skewed pattern). We conclude that skewing of X inactivation in elderly females may be influenced by a locus linked to the G6PD region, most probably through a selection mechanism.
In females one of the two X chromosomes is inactivated in early embryonic life, thus making females mosaics for two cell lines. A skewed X inactivation is a deviation from a 50:50 distribution of these two cell lines. Patients with invasive ovarian cancer were recently shown to have a higher frequency of skewed X inactivation pattern compared to patients with borderline cancer and healthy controls, indicating that skewed X inactivation is a predisposing factor for the development of invasive ovarian cancer. We have analysed X inactivation pattern in peripheral blood from 181 patients with sporadic breast cancer aged 27-90 years. X inactivation was classified as skewed when 90% or more of the peripheral blood cells preferentially used one X-chromosome. Ten per cent of the patients had a skewed X inactivation. Since older females have a higher frequency of skewed X inactivation in peripheral blood cells than young females, young and old patients were analysed separately. The frequency of skewed X inactivation in 34 young patients (27-45 years) was significantly higher than in blood donors of the same age group (12% and 2% respectively, p=0.03). Among 34 old patients (73-90 years), 15% had a skewed X inactivation. This did not differ from the frequency in a population of control females of similar age (21%). Females with a skewed X inactivation pattern may be more susceptible to develop breast cancer due to an X-linked low penetrance susceptibility allele that is affected by the X inactivation pattern.