| 1. |
- Merino, Jordi, et al.
(författare)
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Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium
- 2019
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 24:12, s. 1920-1932
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Tidskriftsartikel (refereegranskat)abstract
- Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10−6) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.
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| 2. |
- Zeng, Jinyan, et al.
(författare)
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導論
- 2022
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Ingår i: 在幽昏中顯影 : 港中對話中國獨立紀錄片 2014-2020 - 港中對話中國獨立紀錄片 2014-2020. - 9781738705009 ; , s. 12-26
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Bokkapitel (refereegranskat)abstract
- 《在幽昏中顯影：港中對話中國獨立紀錄片2014-2020》一書以導演、學者、觀眾對話的形式，討論了中國獨立紀錄片研究會（香港）2014至2020年期間展映、製片、發行的獨立電影。我們從中選擇了記錄較為完整的“叛逆中國”、“飛越瘋人院”、“情慾中國”三個展映單元的獨立紀錄片討論，以及針對夾邊溝右派農場倖存者記憶、維吾爾和新疆議題、三自教會、地下知識分子、前政府高官、工人抗爭等18部影片的映後交流文本或者導演訪談文本，形成本書“性、性別與女性主體”、“權利與政治”、“歷史與記憶”、“放逐與流亡”四個部分的主要內容。本書還收入研究會參與製片的《喊叫與耳語》首映對談，曾金燕對艾未未在跨國視野（流亡處境）下關於藝術（如《人流》）、社會行動和審查的兩次訪談，曾金燕對應亮半自傳劇情片《自由行》的訪談、曾金燕對艾曉明關於性別、紀錄片和社會行動的訪談、曾金燕與王月眉關於在香港八年“邊緣”經驗的筆談。額外收入的稿件中，除卻艾未未訪談，其餘四篇對話，回應獨立電影（本書中主要指紀錄片）的文化生產、策展交流，紀錄片作為社會行動，以及影像研究的智識與藝術傳統裡性別不對等的問題。後三篇回應香港在2014年雨傘運動、2019年反送中運動以及2020年引入國安法後，放逐、流亡到香港的創作者面臨的再次流亡的議題。流亡在這裡，既指內在的、思想的、立場上遠離權力中心的、處於社會邊緣批判既定結構的作者狀態，也指創作者主動或被迫選擇的肉身離開故土的流亡。“權利與政治”討論去政治化的紀錄片電影主流思考方式下，獨立紀錄片對中國社會現實在議題與美學方面的回應，以及關於人的尊嚴如何建構了紀錄片的人文關懷。 “歷史與記憶”章節裡，在通過控制記憶來控制歷史再現的環境中，紀錄片導演和觀眾共同探討了當歷史被壓抑、篡改時，如何找（不）到個人的語言來說（不）出個人的經歷，建構基於個體經驗的、被壓抑的、表演性的個人記憶和集體歷史。將在幽昏中被隱沒的聲音和形象帶到香港的華文世界以及英語世界關於中國的討論中。這，也許就是中國獨立紀錄片研究會在香港所做的工作以及本書的意義。「導論」可通過鏈接免費預覽。This book discusses the independent films screened, produced, and distributed by the China Independent Documentary Lab (Hong Kong) from 2014 to 2020, in conversations between directors, scholars and audiences. This collection has chosen to discuss the relatively well documented independent documentaries in the three screening sections of Rebel China, One Flew Over the Cuckoo's Nest and Desiring China. The book also includes 18 post-screening discussion texts or director interviews on issues on the survivors’ testimonies of Jiabiangou Rightist Labour Camp, Uyghur and Tibetan issues, the three self-churches, the underground intellectuals, former senior government officials, and workers' resistance. The book is composed of four sections: "Sexuality, Gender, and the Female Subjectivity", "Rights and Politics", "History and Memory", and "Banishment and Exile". The book also includes a conversation during the premiere of Outcry and Whisper, which was produced by the CIDL; two interviews by Zeng Jinyan with Ai Weiwei on art (e.g. Human Flow), activism, and censorship in a transnational/exile perspective; an interview by Zeng Jinyan with Ying Liang's semi-autobiographical fiction film Family Tour; an interview by Zeng Jinyan with Ai Xiaoming on gender and documentary film and activism; a written interview by Vivian Wang with Zeng Jinyan on Zeng’s eight years experiences in Hong Kong on the edge.Except the interview with Ai Weiwei, the remaining four conversations respond to the gender asymmetrical tradition of intellectual and art, in cultural production of independent film (mainly documentaries in this book), curatorial exchange, documentary as social action, and documentary studies. The latter three conversations respond to the topic of re-exile faced by artists who had exiled to Hong Kong, after the Umbrella Movement in 2014, the 2019 Hong Kong Protest, and the 2020 introduction of the National Security Law in Hong Kong. Exile in this context refers to both the internal, ideological, authorial state of being on the margins of society, far from the centre of power and critiquing established structures, as well as the physical exile of artists from their homeland, either of their own accord or by forced choice."Power and Politics" discusses the way in which independent documentaries respond to the social reality of China in terms of issues and aesthetics, and how the dignity of the human being constructs the humanistic concerns of documentary film in the context of a de-politicised way of thinking about documentary film. In the section "History and Memory", the documentary filmmaker and the audience discuss how (not able) to find the language of the individual to speak about personal experiences when history is suppressed and tampered with, and to construct a repressed, performative personal memory and collective history based on individual experiences, in a context of controlling the reproduction of history through the control of memory.Bringing the voices and images that have been hidden in the darkness of the dusk to the Chinese world in Hong Kong and to the discussions about China in the English-speaking world. This, perhaps, is what the China Independent Documentary Lab is doing in Hong Kong and the meaning-making of this book.The Introduction chapter can be read in the book free preview.
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| 3. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 4. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 5. |
- Li, Man, et al.
(författare)
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SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function
- 2017
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Ingår i: Journal of the American Society of Nephrology: JASN. - 1533-3450. ; 28:3, s. 981-994
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1<3.7×10-7), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4×10-8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2-knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.
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| 6. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 7. |
- Lunetta, Kathryn L., et al.
(författare)
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Rare coding variants and X-linked loci associated with age at menarche
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only similar to 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency proteincoding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 x 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P = 9.4 x 10(-13)) and FAAH2 (rs5914101, P = 4.9 x 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P = 2.8 x 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain similar to 0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
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| 8. |
- Manning, Alisa, et al.
(författare)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 9. |
- Qi, Qibin, et al.
(författare)
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FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
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Tidskriftsartikel (refereegranskat)abstract
- FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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| 10. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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