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1.	Forsberg, Lars A., et al. (author) Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer 2014 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:6, s. 624-628 Journal article (peer-reviewed)abstract Incidence and mortality for sex-unspecific cancers are higher among men, a fact that is largely unexplained(1,2). Furthermore, age-related loss of chromosome Y (LOY) is frequent in normal hematopoietic cells(3,4), but the phenotypic consequences of LOY have been elusive(5-10). From analysis of 1,153 elderly men, we report that LOY in peripheral blood was associated with risks of all-cause mortality (hazards ratio (HR) = 1.91, 95% confidence interval (CI) = 1.17-3.13; 637 events) and non-hematological cancer mortality (HR = 3.62, 95% CI = 1.56-8.41; 132 events). LOY affected at least 8.2% of the subjects in this cohort, and median survival times among men with LOY were 5.5 years shorter. Association of LOY with risk of all-cause mortality was validated in an independent cohort (HR = 3.66) in which 20.5% of subjects showed LOY. These results illustrate the impact of post-zygotic mosaicism on disease risk, could explain why males are more frequently affected by cancer and suggest that chromosome Y is important in processes beyond sex determination. LOY in blood could become a predictive biomarker of male carcinogenesis.
2.	Scott, Robert A., et al. (author) Common Genetic Variants Highlight the Role of Insulin Resistance and Body Fat Distribution in Type 2 Diabetes, Independent of Obesity 2014 In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:12, s. 4378-4387 Journal article (peer-reviewed)abstract We aimed to validate genetic variants as instruments for insulin resistance and secretion, to characterize their association with intermediate phenotypes, and to investigate their role in type 2 diabetes (T2D) risk among normal-weight, overweight, and obese individuals. We investigated the association of genetic scores with euglycemic-hyperinsulinemic clamp- and oral glucose tolerance test-based measures of insulin resistance and secretion and a range of metabolic measures in up to 18,565 individuals. We also studied their association with T2D risk among normal-weight, overweight, and obese individuals in up to 8,124 incident T2D cases. The insulin resistance score was associated with lower insulin sensitivity measured by M/I value (beta in SDs per allele [95% CI], -0.03 [-0.04, -0.01]; P = 0.004). This score was associated with lower BMI (-0.01 [-0.01, -0.0]; P = 0.02) and gluteofemoral fat mass (-0.03 [-0.05,-0.02; P = 1.4x10(-6) and with higher alanine transaminase (0.02 [0.01, 0.03]; P = 0.002) and gamma-glutamyl transferase (0.02 [0.01, 0.03]; P = 0.001). While the secretion score had a stronger association with T2D in leaner individuals (P-interaction = 0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI or waist strata (P-interaction > 0.31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of body size.
3.	Wood, AR, et al. (author) Defining the role of common variation in the genomic and biological architecture of adult human height 2014 In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:11, s. 1173-1186 Journal article (peer-reviewed)

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Type of publication: journal article (3)

Type of content: peer-reviewed (3)

Author/Editor: Franks, Paul (2); Groop, Leif (2); Lind, Lars (2); Brambilla, P (1); Erdmann, J. (1); Kaprio, J (1); show more...; Peters, A (1); Silventoinen, K (1); Mahajan, A. (1); Sinisalo, J. (1); Roswall, Nina (1); Baron, J (1); Luan, J. (1); Cooper, M. (1); Kivimaki, M (1); Overvad, Kim (1); Clavel-Chapelon, Fra ... (1); Fagherazzi, Guy (1); Kaaks, Rudolf (1); Boeing, Heiner (1); Tumino, Rosario (1); Sacerdote, Carlotta (1); Sánchez, Maria-José (1); Barricarte, Aurelio (1); Key, Timothy J (1); Riboli, Elio (1); Rolandsson, Olov (1); Langenberg, C. (1); Tanaka, T. (1); Collins, R (1); Berne, Christian (1); Nilsson, Peter (1); Boomsma, DI (1); Pedersen, NL (1); Amin, N (1); van Duijn, CM (1); Yang, J. (1); Ford, I. (1); Johansson, A (1); Loos, RJF (1); Lorentzon, Mattias, ... (1); Walker, M (1); Fischer, K. (1); Lyssenko, V. (1); Magnusson, PKE (1); Hall, P (1); Lannfelt, Lars (1); Albrecht, E (1); Hoffmann, P (1); Trompet, S (1); show less...

University: Uppsala University (3); Umeå University (2); Lund University (2); Karolinska Institutet (2); University of Gothenburg (1); Högskolan Dalarna (1)

Language: English (3)

Research subject (UKÄ/SCB): Medical and Health Sciences (3)

Year: 2014 (3)

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