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      Enrichment of minor allele of SNPs and genetic prediction of type 2 diabetes risk in British population

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          Abstract

          Type 2 diabetes (T2D) is a complex disorder characterized by high blood sugar, insulin resistance, and relative lack of insulin. The collective effects of genome wide minor alleles of common SNPs, or the minor allele content (MAC) in an individual, have been linked with quantitative variations of complex traits and diseases. Here we studied MAC in T2D using previously published SNP datasets and found higher MAC in cases relative to matched controls. A set of 357 SNPs was found to have the best predictive accuracy in a British population. A weighted risk score calculated by using this set produced an area under the curve (AUC) score of 0.86, which is comparable to risk models built by phenotypic markers. These results identify a novel genetic risk element in T2D susceptibility and provide a potentially useful genetic method to identify individuals with high risk of T2D.

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          Most cited references14

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          Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.

          By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
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            The genetic structure and history of Africans and African Americans.

            Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (approximately 71%), European (approximately 13%), and other African (approximately 8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies.
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              Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis.

              Observational studies have suggested an association between active smoking and the incidence of type 2 diabetes. To conduct a systematic review with meta-analysis of studies assessing the association between active smoking and incidence of type 2 diabetes. A search of MEDLINE (1966 to May 2007) and EMBASE (1980 to May 2007) databases was supplemented by manual searches of bibliographies of key retrieved articles, reviews of abstracts from scientific meetings, and contact with experts. Studies were included if they reported risk of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes in relationship to smoking status at baseline; had a cohort design; and excluded persons with diabetes at baseline. Two authors independently extracted the data, including the presence or absence of active smoking at baseline, the risk of diabetes, methods used to detect diabetes, and key criteria of study quality. Relative risks (RRs) were pooled using a random-effects model. Associations were tested in subgroups representing different patient characteristics and study quality criteria. The search yielded 25 prospective cohort studies (N = 1.2 million participants) that reported 45 844 incident cases of diabetes during a study follow-up period ranging from 5 to 30 years. Of the 25 studies, 24 reported adjusted RRs greater than 1 (range for all studies, 0.82-3.74). The pooled adjusted RR was 1.44 (95% confidence interval [CI], 1.31-1.58). Results were consistent and statistically significant in all subgroups. The risk of diabetes was greater for heavy smokers (> or =20 cigarettes/day; RR, 1.61; 95% CI, 1.43-1.80) than for lighter smokers (RR,1.29; 95% CI, 1.13-1.48) and lower for former smokers (RR, 1.23; 95% CI, 1.14-1.33) compared with active smokers, consistent with a dose-response phenomenon. Active smoking is associated with an increased risk of type 2 diabetes. Future research should attempt to establish whether this association is causal and to clarify its mechanisms.
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                Author and article information

                Contributors
                Role: Writing – original draft
                Role: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                3 November 2017
                2017
                : 12
                : 11
                : e0187644
                Affiliations
                [001]Laboratory of Medical Genetics, School of Life Sciences, Xiangya Medical School, Central South University, Changsha, Hunan, China
                Universita degli Studi di Roma La Sapienza, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-2674-2830
                Article
                PONE-D-17-31678
                10.1371/journal.pone.0187644
                5669465
                29099854
                649f184b-035d-48d5-8e86-1277d162149f
                © 2017 Lei, Huang

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 August 2017
                : 23 October 2017
                Page count
                Figures: 3, Tables: 3, Pages: 13
                Funding
                This work was supported by the National Natural Science Foundation of China [S.H. received the funding and grant number was 81171880]; the National Basic Research Program of China [S.H. received the funding and grant number was 2011CB51001]; and the research grant for postgraduate students provided by the Central South University of China [X.L. received the funding and grant number was 2017zzts375]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Forecasting
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Forecasting
                Biology and Life Sciences
                Biochemistry
                Lipids
                Cholesterol
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Multivariate Analysis
                Principal Component Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Multivariate Analysis
                Principal Component Analysis
                Biology and Life Sciences
                Computational Biology
                Genome Analysis
                Genome-Wide Association Studies
                Biology and Life Sciences
                Genetics
                Genomics
                Genome Analysis
                Genome-Wide Association Studies
                Biology and Life Sciences
                Genetics
                Human Genetics
                Genome-Wide Association Studies
                Biology and Life Sciences
                Behavior
                Habits
                Smoking Habits
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Body Mass Index
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Body Mass Index
                Biology and Life Sciences
                Genetics
                Heredity
                Complex Traits
                Custom metadata
                All WTCCC samples are available from the https://www.wtccc.org.uk/ database. All phs000091 samples are available from the https://www.ncbi.nlm.nih.gov/gap database (accession number: phs000091.v2.p1).

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