Sök i LIBRIS databas

  Utökad sökning


Sökning: onr:"swepub:oai:DiVA.org:umu-142914" > Identification of G...

Identification of Genetic Loci Jointly Influencing Schizophrenia Risk and the Cognitive Traits of Verbal-Numerical Reasoning, Reaction Time, and General Cognitive Function

Smeland, Olav B. (författare)
Frei, Oleksandr (författare)
Kauppi, Karolina (författare)
Umeå universitet,Institutionen för strålningsvetenskaper,Department of Radiology, University of California San Diego, La Jolla; Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla
visa fler...
Hill, W. David (författare)
Li, Wen (författare)
Wang, Yunpeng (författare)
Krull, Florian (författare)
Bettella, Francesco (författare)
Eriksen, Jon A. (författare)
Witoelar, Aree (författare)
Davies, Gail (författare)
Fan, Chun C. (författare)
Thompson, Wesley K. (författare)
Lam, Max (författare)
Lencz, Todd (författare)
Chen, Chi-Hua (författare)
Ueland, Torill (författare)
Jönsson, Erik G. (författare)
Djurovic, Srdjan (författare)
Deary, Ian J. (författare)
Dale, Anders M. (författare)
Andreassen, Ole A. (författare)
Smeland, OB (författare)
Fan, CC (författare)
Krull, F (författare)
Witoelar, A (författare)
Deary, IJ (författare)
Bettella, F (författare)
Davies, G (författare)
Lam, M (författare)
Li, W (författare)
Kauppi, K (författare)
Hill, WD (författare)
Ueland, T (författare)
Chen, CH (författare)
Andreassen, OA (författare)
Djurovic, S (författare)
Lencz, T (författare)
Jonsson, EG (författare)
Karolinska Institutet
Thompson, WK (författare)
Frei, O (författare)
Eriksen, JA (författare)
Wang, YP (författare)
Dale, AM (författare)
visa färre...
American Medical Association, 2017
Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 74:10, s. 1065-1075
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
  • IMPORTANCE Schizophrenia is associated with widespread cognitive impairments. Although cognitive deficits are one of the factors most strongly associated with functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these impairments. To develop more efficient treatment strategies in patients with schizophrenia, a better understanding of the pathogenesis of these cognitive deficits is needed. Accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction. OBJECTIVE To identify genomic regions jointly influencing schizophrenia and the cognitive domains of reaction time and verbal-numerical reasoning, aswell as general cognitive function, a phenotype that captures the shared variation in performance across cognitive domains. DESIGN, SETTING, AND PARTICIPANTS Combining data from genome-wide association studies from multiple phenotypes using conditional false discovery rate analysis provides increased power to discover genetic variants and could elucidate shared molecular genetic mechanisms. Data from the following genome-wide association studies, published from July 24, 2014, to January 17, 2017, were combined: schizophrenia in the Psychiatric Genomics Consortium cohort (n = 79 757 [ cases, 34 486; controls, 45 271]); verbal-numerical reasoning (n = 36 035) and reaction time (n = 111 483) in the UK Biobank cohort; and general cognitive function in CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) (n = 53 949) and COGENT (Cognitive Genomics Consortium) (n = 27 888). MAIN OUTCOMES AND MEASURES Genetic loci identified by conditional false discovery rate analysis. Brain messenger RNA expression and brain expression quantitative trait locus functionality were determined. RESULTS Among the participants in the genome-wide association studies, 21 loci jointly influencing schizophrenia and cognitive traits were identified: 2 loci shared between schizophrenia and verbal-numerical reasoning, 6 loci shared between schizophrenia and reaction time, and 14 loci shared between schizophrenia and general cognitive function. One locus was shared between schizophrenia and 2 cognitive traits and represented the strongest shared signal detected (nearest gene TCF20; chromosome 22q13.2), and was shared between schizophrenia (z score, 5.01; P = 5.53 x 10(-7)), general cognitive function (z score, - 4.43; P = 9.42 x 10(-6)), and verbal-numerical reasoning (z score, - 5.43; P = 5.64 x 10(-8)). For 18 loci, schizophrenia risk alleles were associated with poorer cognitive performance. The implicated genes are expressed in the developmental and adult human brain. Replicable expression quantitative trait locus functionality was identified for 4 loci in the adult human brain. CONCLUSIONS AND RELEVANCE The discovered loci improve the understanding of the common genetic basis underlying schizophrenia and cognitive function, suggesting novel molecular genetic mechanisms.


MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Publikations- och innehållstyp

ref (ämneskategori)
art (ämneskategori)

Hitta via bibliotek

Till lärosätets databas

pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy