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5. Development and characterization of kevlar and glass fibers reinforced epoxy/vinyl ester hybrid resin composites

Author

Ahmad, Hammad, Shah, Atta Ur Rehman, Afaq, S. Kamran, Azad, Muhammad Muzammil, Arif, Saad, Siddiqi, Muftooh Ur Rehman, Xie, Lijing, Ahmad, Hammad, Shah, Atta Ur Rehman, Afaq, S. Kamran, Azad, Muhammad Muzammil, Arif, Saad, Siddiqi, Muftooh Ur Rehman, and Xie, Lijing

Abstract

This research investigates the influence of kevlar and glass fiber reinforcements on the mechanical and thermal properties of epoxy/vinyl ester (hybrid resin) composite. The hybrid resin was synthesized by achieving an interpenetrating network between epoxy and vinyl ester. The composites were characterized using tensile, flexural, impact, and thermo‐gravimetric analysis (TGA). Scanning electron microscopy was employed to analyze surface morphology whereas Fourier‐Transformation Infrared Spectroscopy (FT‐IR) was used to investigate the possible interaction between the constituents of the composites. The findings have shown a notable improvement in the mechanical properties after the hybridization of the resin. For reference, the tensile strength of glass/hybrid resin and kevlar/hybrid resin composites were observed to increase by 8.33% and 23.65%, as compared to glass/epoxy and kevlar epoxy composites respectively, whereas, the bending strength of these composites was improved by 8.36% and 30.61%, respectively. TGA also showed an enhanced thermal stability of the hybrid resin‐based composites. Such improvements are noticed due to multi‐resin incorporation (the oxirane group of epoxy reacts with the hydroxyl group of vinyl ester), confirmed by the FTIR, TGA, and morphological analysis. This study signifies that the proposed hybrid composites are better in terms of strength and modulus relative to conventional metallic materials.

Published
2024

8. Association and comparison of periodontal and oral hygiene status with serum HbA1c levels: a cross-sectional study

Author

Afaq, S

Abstract

Background: Diabetes Mellitus and periodontitis are chronic diseases with known reciprocal association. Studies have shown that uncontrolled diabetes increases the risk of development and progression of periodontal disease. This study aimed to explore the association and severity of periodontal clinical parameters and oral hygiene with HbA1c levels in non-diabetics and T2DM patients. Materials and Methods: In this cross-sectional study, the periodontal status of 144 participants, categorized into non-diabetics, controlled T2DM, and uncontrolled T2DM and were assessed via the Community Periodontal Index (CPI), Loss of Attachment Index (LOA index), and the number of missing teeth, while oral hygiene was measured by utilizing the Oral Hygiene Index Simplified (OHI-S). SPSS was used for data analysis. Chi-square test was used to find out the association of different independent variables with HbA1c groups, while ANOVA and post-hoc tests were run for inter-group and intra-group comparison respectively. Results: Out of 144 participants, the missing dentition was prevalent in uncontrolled T2DM with mean 2.64±1.97 (95% CI 2.07 – 3.21; p = 0.01) followed by controlled T2DM 1.70±1.79 (95% CI 1.18- 2.23; p = 0.01) and non-diabetics 1.35±1.63 (95% CI 0.88 – 1.82; p = 0.01) respectively. Furthermore, non38 diabetics had a higher proportion of CPI score 0 (Healthy) [30 (20.8%); p=0.001] as compared to uncontrolled T2DM [6 (4.2%); p=0.001], while CPI score 3 was more prevalent in uncontrolled T2DM in comparison to non-diabetics. Loss of attachment (codes-2,3 and 4) was also frequently observed in uncontrolled T2DM compared to non-diabetics (p=0.001). Similarly, based on Oral Hygiene Index Simplified (OHI-S), the result showed that poor oral hygiene was most commonly observed in uncontrolled T2DM 29 (20.1%) followed by controlled T2DM patients 22 (15.3%) and non-diabetic [14 (9.7%); p=0.03]. Conclusion: This study showed that periodontal status and oral hygiene status deteriorated in uncontrolled T2DM patients compared to non-diabetic participants and controlled T2DM. Keywords: Periodontitis; diabetes mellitus; probe; bleeding on probing; pocket depth; loss of attachment.

Published
2023

10. Frictional performance of chemically modified cottonseed-based fossil-free biolubricant oil in a sliding tribopair

Author

Ghumman, I. S. S., Afaq, S. K., Usman, Ali, Ghumman, I. S. S., Afaq, S. K., and Usman, Ali

Abstract

In this study, the tribological properties of a green lubricant synthesized from cottonseed oil through a two-step transesterification process are investigated, with a specific focus on the maximum throughput of the second step that involves the reaction of cottonseed methyl ester with 2-ethyl-1-hexanol alcohol and a titanium isopropoxide (TIS) catalyst. The research centers on evaluating the physiochemical characteristics of this biolubricant and comparing them with those of commercial oil (5W30) and the ISO VG40 standard. Furthermore, the influence of crucial process variables, such as temperature, pressure, reaction time, and TIS catalyst concentration, is examined by analyzing variance in experimental data. Fourier transform infrared (FTIR) analysis is employed to identify functional groups, particularly emphasizing the impact of temperature and reaction time. By optimizing the second transesterification process under specific conditions (pressure = 19.42 mmHg, temperature = 175°C, catalyst concentration = 0.63%, and reaction time = 4.0 h), a cottonseed oil-based biolubricant is successfully produced, exhibiting properties comparable to those of commercial mineral lubricants. Notably, the findings reveal significant enhancements in the coefficient of friction (CoF) with a 49% reduction and wear resistance with a maximum 19% reduction. This study contributes valuable insights into optimizing biolubricant production derived from cottonseed oil through two-step transesterification, emphasizing its novel potential in improving frictional and wear characteristics., Validerad;2023;Nivå 2;2023-10-25 (johcin);CC BY 4.0 License

Published
2023
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12. Metabolic Health Profile of Employees in a Printing Press in Peshawar, Pakistan

Author

Afaq, S, Ali, M, Ahmad, M, Hussain, S, Ali, W, and Munir, I

Subjects
Health (social science), Physiology, 1302 Curriculum and Pedagogy, Rehabilitation, 1106 Human Movement and Sports Sciences, Biomedical Engineering, Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine, Public Health, Anatomy, 1117 Public Health and Health Services
Abstract

Background: Printing press workers deal with printing inks that contain potentially hazardous chemicals and solvents. Present study was designed to determine the biochemical health profile of printing press workers. Methods: Cross sectional study was conducted in 50 printing press (male) workers and 20 non-printing press age matched (male) workers, who were not exposed to printing press environment but lived all around the printing press area. Non-fasting blood samples were collected, from both Workers and Non-Workers, for determining full blood counts, lipid profile, Uric acid and Creatinine. Results: Mean levels of cholesterol was 213 mg/dl (SD = ±13.0) vs 146 (SD = ±5.50), P = 0.04], triglycerides were 303 mg/dl (SD = ±16.9) vs 196 mg/dl (SD = ±7.13), P = 0.03 and LDL was 103 mmol/l (±3.32) vs 42.9 mmol/l (±2.57), P = 0.01 which were significantly higher in printing press workers than in Nonworkers. Additionally, mean total leukocyte count and total lymphocytes, were significantly higher 8590 (SD = ±830) vs. 7100 (SD = ±542) per cmm, P = 0.04 and 44.8 (SD = ±2.17) % vs. 33.1 (SD = ±1.85)% respectively, P = 0.02) while mean neutrophil count was significantly lower 46.3% (SD ± 1.97) vs. 59.7 % (SD ± 1.88) respectively, P = 0.03 in printing press workers than in Nonworkers. Conclusion: Exposure to various chemicals in inks may put printing press workers at risk of poor biochemical profile which is an important risk factor for developing non-communicable diseases.

Published
2022

13. PREPARATION OF CORROSION INHIBITORS BASED ON SOME CARBO AND HETEROCYCLIC COMPOUNDS

Author

Zeynalov, E., Afaq, S., and Mammedova, R.

Subjects
corrosion, corrosion inhibitors, heterocyclic compounds
Abstract

Our goal is to synthesize stable corrosion inhibitors to prevent corrosion, which is one of the most important problems of today. During the synthesis of these compounds, first of all, we need to ensure a more harmless, more convenient way and financially more profitable process of obtaining these compounds. To clarify the synthesis of corrosion inhibitors used to prevent corrosion and whether those inhibitors are useful, we must first examine what corrosion and corrosion inhibitors are. Information about them is given in a certain part of the article. Then, the most commonly used corrosion inhibitors and their synthesis were discussed.

Published
2023
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18. Arthroplasty versus internal fixation for the treatment of undisplaced femoral neck fractures

Author

Afaq, S., OʼHara, N.N., Schemitsch, E.H., Bzovsky, S., Sprague, S., Poolman, R.W., Frihagen, F., Heels-Ansdell, D., Bhandari, M., Tan, E.C.T.H., Kampen, A. van, Biert, J., Edwards, M.J.R., Frolke, J.P.M., Poelhekke, L.M.S.J., Waal Malefijt, M.C. de, Schreurs, B.W., Swiontkowski, M., and Slobogean, G.P.

Subjects
Male, Reoperation, medicine.medical_specialty, medicine.medical_treatment, Arthroplasty, Replacement, Hip, Femoral Neck Fractures, law.invention, 03 medical and health sciences, Fracture Fixation, Internal, 0302 clinical medicine, Randomized controlled trial, law, medicine, Risk of mortality, internal fixation, Internal fixation, Humans, Orthopedics and Sports Medicine, undisplaced femoral neck fracture, Aged, Retrospective Studies, Aged, 80 and over, 030222 orthopedics, business.industry, Mortality rate, 030208 emergency & critical care medicine, Retrospective cohort study, General Medicine, Odds ratio, Middle Aged, Arthroplasty, Surgery, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], Treatment Outcome, Quality of Life, arthroplasty, Female, Hemiarthroplasty, business
Abstract

Contains fulltext : 228684.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To compare the 24-month risk of mortality between arthroplasty and internal fixation for undisplaced femoral neck fractures (FNFs). DESIGN: Retrospective cohort study. SETTING: Secondary data analysis of 2 multinational randomized controlled trials. PARTICIPANTS: Patients aged 50 years or older with a FNF. INTERVENTION: Arthroplasty (n = 1441), including total hip arthroplasty and hemiarthroplasty, performed for a displaced FNF versus internal fixation (n = 734), including sliding hip screw or multiple cancellous screws, performed for an undisplaced FNF. MAIN OUTCOME MEASUREMENT: The primary outcome was mortality within 24 months of injury. Secondary outcomes included reoperation and health-related quality of life. RESULTS: The 24-month mortality rate was 15.0% (n = 327). Arthroplasty was associated with a significant reduction in the odds of mortality [adjusted odds ratio (aOR): 0.56, 95% confidence interval (CI): 0.44-0.72, P < 0.01] compared with treatment with internal fixation. 11.4% (n = 248) of the study patients required reoperation within 24 months of injury. The odds of reoperation were 59% lower with arthroplasty treatment than with internal fixation (aOR: 0.41, 95% CI: 0.32-0.55, P < 0.01). The 24-month SF-12 physical component scores were 2.7 points higher in arthroplasty patients compared with internal fixation patients (95% CI: 1.6-3.8, P < 0.01). CONCLUSIONS: Our findings suggest arthroplasty for a FNF may reduce the risk of mortality and reoperation compared with internal fixation of undisplaced fractures. This finding is counter to many current surgical practices but consistent with a mounting body of evidence. Before widespread adoption of arthroplasty for undisplaced fractures, these results should be confirmed in a definitive comparative trial. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Published
2020

19. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Author

Erzurumluoglu, AM, Liu, M, Jackson, VE, Barnes, DR, Datta, G, Melbourne, CA, Young, R, Batini, C, Surendran, P, Jiang, T, Adnan, SD, Afaq, S, Agrawal, A, Altmaier, E, Antoniou, AC, Asselbergs, FW, Baumbach, C, Beirut, L, Bertelsen, S, Boehnke, M, Bots, ML, Brazel, DM, Chambers, JC, Chang-Claude, J, Chen, C, Corley, J, Chou, Y-L, David, SP, de Boer, RA, de Leeuw, CA, Dennis, JG, Dominiczak, AF, Dunning, AM, Easton, DF, Eaton, C, Elliott, P, Evangelou, E, Faul, JD, Foroud, T, Goate, A, Gong, J, Grabe, HJ, Haessler, J, Haiman, C, Hallmans, G, Hammerschlag, AR, Harris, SE, Hattersley, A, Heath, A, Hsu, C, Iacono, WG, Kanoni, S, Kapoor, M, Kaprio, J, Kardia, SL, Karpe, F, Kontto, J, Kooner, JS, Kooperberg, C, Kuulasmaa, K, Laakso, M, Lai, D, Langenberg, C, Le, N, Lettre, G, Loukola, A, Luan, J, Madden, PAF, Mangino, M, Marioni, RE, Marouli, E, Marten, J, Martin, NG, McGue, M, Michailidou, K, Mihailov, E, Moayyeri, A, Moitry, M, Müller-Nurasyid, M, Naheed, A, Nauck, M, Neville, MJ, Nielsen, SF, North, K, Perola, M, Pharoah, PDP, Pistis, G, Polderman, TJ, Posthuma, D, Poulter, N, Qaiser, B, Rasheed, A, Reiner, A, Renström, F, Rice, J, Rohde, R, Rolandsson, O, Samani, NJ, Samuel, M, Schlessinger, D, Scholte, SH, Scott, RA, Sever, P, Shao, Y, Shrine, N, Smith, JA, Starr, JM, Stirrups, K, Stram, D, Stringham, HM, Tachmazidou, I, Tardif, J-C, Thompson, DJ, Tindle, HA, Tragante, V, Trompet, S, Turcot, V, Tyrrell, J, Vaartjes, I, van der Leij, AR, van der Meer, P, Varga, TV, Verweij, N, Völzke, H, Wareham, NJ, Warren, HR, Weir, DR, Weiss, S, Wetherill, L, Yaghootkar, H, Yavas, E, Jiang, Y, Chen, F, Zhan, X, Zhang, W, Zhao, W, Zhou, K, Amouyel, P, Blankenberg, S, Caulfield, MJ, Chowdhury, R, Cucca, F, Deary, IJ, Deloukas, P, Di Angelantonio, E, Ferrario, M, Ferrières, J, Franks, PW, Frayling, TM, Frossard, P, Hall, IP, Hayward, C, Jansson, J-H, Jukema, JW, Kee, F, Männistö, S, Metspalu, A, Munroe, PB, Nordestgaard, BG, Palmer, CNA, Salomaa, V, Sattar, N, Spector, T, Strachan, DP, Understanding Society Scientific Group, EPIC-CVD, GSCAN, Consortium for Genetics of Smoking Behaviour, CHD Exome+ Consortium, van der Harst, P, Zeggini, E, Saleheen, D, Butterworth, AS, Wain, LV, Abecasis, GR, Danesh, J, Tobin, MD, Vrieze, S, Liu, DJ, and Howson, JMM

Abstract

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P

Published
2020

20. Arthroplasty Versus Internal Fixation for the Treatment of Undisplaced Femoral Neck Fractures: A Retrospective Cohort Study

Author

Afaq, S., OʼHara, N.N., Schemitsch, E.H., Bzovsky, S., Sprague, S., Poolman, R.W., Frihagen, F., Heels-Ansdell, D., Bhandari, M., Tan, E.C.T.H., Kampen, A. van, Biert, J., Edwards, M.J.R., Frolke, J.P.M., Poelhekke, L.M.S.J., Waal Malefijt, M.C. de, Schreurs, B.W., Swiontkowski, M., Slobogean, G.P., Afaq, S., OʼHara, N.N., Schemitsch, E.H., Bzovsky, S., Sprague, S., Poolman, R.W., Frihagen, F., Heels-Ansdell, D., Bhandari, M., Tan, E.C.T.H., Kampen, A. van, Biert, J., Edwards, M.J.R., Frolke, J.P.M., Poelhekke, L.M.S.J., Waal Malefijt, M.C. de, Schreurs, B.W., Swiontkowski, M., and Slobogean, G.P.

Abstract

Contains fulltext : 228684.pdf (Publisher’s version ) (Closed access), OBJECTIVE: To compare the 24-month risk of mortality between arthroplasty and internal fixation for undisplaced femoral neck fractures (FNFs). DESIGN: Retrospective cohort study. SETTING: Secondary data analysis of 2 multinational randomized controlled trials. PARTICIPANTS: Patients aged 50 years or older with a FNF. INTERVENTION: Arthroplasty (n = 1441), including total hip arthroplasty and hemiarthroplasty, performed for a displaced FNF versus internal fixation (n = 734), including sliding hip screw or multiple cancellous screws, performed for an undisplaced FNF. MAIN OUTCOME MEASUREMENT: The primary outcome was mortality within 24 months of injury. Secondary outcomes included reoperation and health-related quality of life. RESULTS: The 24-month mortality rate was 15.0% (n = 327). Arthroplasty was associated with a significant reduction in the odds of mortality [adjusted odds ratio (aOR): 0.56, 95% confidence interval (CI): 0.44-0.72, P < 0.01] compared with treatment with internal fixation. 11.4% (n = 248) of the study patients required reoperation within 24 months of injury. The odds of reoperation were 59% lower with arthroplasty treatment than with internal fixation (aOR: 0.41, 95% CI: 0.32-0.55, P < 0.01). The 24-month SF-12 physical component scores were 2.7 points higher in arthroplasty patients compared with internal fixation patients (95% CI: 1.6-3.8, P < 0.01). CONCLUSIONS: Our findings suggest arthroplasty for a FNF may reduce the risk of mortality and reoperation compared with internal fixation of undisplaced fractures. This finding is counter to many current surgical practices but consistent with a mounting body of evidence. Before widespread adoption of arthroplasty for undisplaced fractures, these results should be confirmed in a definitive comparative trial. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Published
2020

21. Arthroplasty Versus Internal Fixation for the Treatment of Undisplaced Femoral Neck Fractures: A Retrospective Cohort Study

Author

Afaq, S. (Shaikh), O'Hara, N.N. (Nathan), Schemitsch, E.H. (Emil), Bzovsky, S. (Sofia), Sprague, S. (Sheila), Poolman, R.W. (Rudolf), Frihagen, F. (Frede), Heels-Ansdell, D. (Diane), Bhandari, M. (Mohit), Swiontkowski, M.F. (Marc ), Slobogean, G.P. (Gerard), Afaq, S. (Shaikh), O'Hara, N.N. (Nathan), Schemitsch, E.H. (Emil), Bzovsky, S. (Sofia), Sprague, S. (Sheila), Poolman, R.W. (Rudolf), Frihagen, F. (Frede), Heels-Ansdell, D. (Diane), Bhandari, M. (Mohit), Swiontkowski, M.F. (Marc ), and Slobogean, G.P. (Gerard)

Abstract

OBJECTIVE: To compare the 24-month risk of mortality between arthroplasty and internal fixation for undisplaced femoral neck fractures (FNFs). DESIGN: Retrospective cohort study. SETTING: Secondary data analysis of 2 multinational randomized controlled trials. PARTICIPANTS: Patients aged 50 years or older with a FNF. INTERVENTION: Arthroplasty (n = 1441), including total hip arthroplasty and hemiarthroplasty, performed for a displaced FNF versus internal fixation (n = 734), including sliding hip screw or multiple cancellous screws, performed for an undisplaced FNF. MAIN OUTCOME MEASUREMENT: The primary outcome was mortality within 24 months of injury. Secondary outcomes included reoperation and health-related quality of life. RESULTS: The 24-month mortality rate was 15.0% (n = 327). Arthroplasty was associated with a significant reduction in the odds of mortality [adjusted odds ratio (aOR): 0.56, 95% confidence interval (CI): 0.44-0.72, P < 0.01] compared with treatment with internal fixation. 11.4% (n = 248) of the study patients required reoperation within 24 months of injury. The odds of reoperation were 59% lower with arthroplasty treatment than with internal fixation (aOR: 0.41, 95% CI: 0.32-0.55, P < 0.01). The 24-month SF-12 physical component scores were 2.7 points higher in arthroplasty patients compared with internal fixation patients (95% CI: 1.6-3.8, P < 0.01). CONCLUSIONS: Our findings suggest arthroplasty for a FNF may reduce the risk of mortality and reoperation compared with internal fixation of undisplaced fractures. This finding is counter to many current surgical practices but consistent with a mounting body of evidence. Before widespread adoption of arthroplasty for undisplaced fractures, these results should be confirmed in a definitive comparative trial. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Published
2020
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23. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Author

Erzurumluoglu, AM, Liu, M, Jackson, VE, Barnes, DR, Datta, G, Melbourne, CA, Young, R, Batini, C, Surendran, P, Jiang, T, Adnan, SD, Afaq, S, Agrawal, A, Altmaier, E, Antoniou, AC, Asselbergs, FW, Baumbach, C, Bierut, L, Bertelsen, S, Boehnke, M, Bots, ML, Brazel, DM, Chambers, JC, Chang-Claude, J, Chen, C, Corley, J, Chou, YL, David, SP, de Boer, RA, de Leeuw, CA, Dennis, JG, Dominiczak, AF, Dunning, AM, Easton, DF, Eaton, C, Elliott, P, Evangelou, E, Faul, JD, Foroud, T, Goate, A, Gong, J, Grabe, HJ, Haessler, J, Haiman, C, Hallmans, G, Hammerschlag, AR, Harris, SE, Hattersley, A, Heath, A, Hsu, C, Iacono, WG, Kanoni, S, Kapoor, M, Kaprio, J, Kardia, SL, Karpe, F, Kontto, J, Kooner, JS, Kooperberg, C, Kuulasmaa, K, Laakso, M, Lai, D, Langenberg, C, Le, N, Lettre, G, Loukola, A, Luan, J, Madden, PAF, Mangino, M, Marioni, RE, Graduate School, Experimental Vascular Medicine, ACS - Diabetes & metabolism, Amsterdam Cardiovascular Sciences, ACS - Atherosclerosis & ischemic syndromes, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Cardiology, Radiotherapy, and Experimental Immunology

Published
2019

24. Associations of autozygosity with a broad range of human phenotypes

Author

Clark, D.W. (David W), Okada, Y. (Yukinori), Moore, K.H.S. (Kristjan H S), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C.L.K. (Catriona L K), Lin, K. (Kuang), Zhao, J.H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, M.C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T.M. (Traci M), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M.J. (Matthew J), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Dekker, A.M. (Annelot M), Eccles, D.A. (David A), Eijk, K.R. (Kristel) van, Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S.D. (Scott D.), de Haan, H.G. (Hugoline G), Harris, S.E. (Sarah), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. (Iris), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M.E. (Marcus), Li, S.A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M.E. (May E.), Most, P.J. (Peter) van der, Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R.B. (Rashmi B), Priyanka, T.D.S. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B.R. (Bishwa R), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M.C. (Melissa C), Smith, A.V. (Albert), Spek, A. (Ashley) van der, Spracklen, C.N. (Cassandra N), Strawbridge, R.J. (Rona), Tajuddin, S.M. (Salman M), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. (Helen), Wootton, R.E. (Robyn E), Yanek, L.R. (Lisa), Yao, J. (Jie), Yousri, N.A. (Noha A), Zhao, W. (Wei), Adeyemo, A.A. (Adebowale A), Afaq, S. (Saima), Aguilar-Salinas, C.A. (Carlos Alberto), Akiyama, M. (Masato), Albert, M.L. (Matthew L), Allison, M.A. (Matthew A), Alver, M. (Maris), Aung, T. (Tin), Azizi, J. (Joshan), Bentley, A.R. (Amy), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Borja, J.B. (Judith B), Borst, G.J. (Gert) de, Bottinger, E.P. (Erwin), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S.J. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y.-D.I. (Yii-Der I), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Concas, M.P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Dam, R.M. (Rob) van, Damulina, A. (Anna), Daneshpour, M.S. (Maryam S), Day, F.R. (Felix), Delgado, G., Dhana, K. (Klodian), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Doumatey, A. (Ayo), Dzimiri, N. (Nduna), Ebenesersdóttir, S.S. (S Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J.F. (Janine), Fischer, K. (Krista), Freedman, B.I. (Barry), Girotto, S., Goel, A. (Anuj), Gögele, M. (Martin), Goodarzi, M. (Mark), Graff, M.J. (Maud J.L.), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S.P. (Saskia P), Haiman, C.A. (Christopher), Halevy, A. (Avner), Harris, T.B. (Tamara B), Hedayati, M. (Mehdi), Heel, D.A. (David) van, Hirata, M. (Makoto), Höfer, I. (Imo), Hsiung, C.A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M.A. (Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N.D. (Nicola D), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C.C., Kleijn, D.P.V. (Dominique) de, Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Krämer, B.K. (Bernhard), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. (M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S.J. (Stephanie J), Loomis, S.J. (Stephanie J.), Lu, Y. (Yingchang), Luan, J. (Jian’an), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X.W. (Xue W), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I.Y. (Iona), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (P.), Moreno-Macías, H. (Hortensia), Mori, T.A. (Trevor A), Morrison, A.C. (Alanna), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A.D. (Alison D), Mutsert, R. (Reneé) de, Mychaleckyj, J.C. (Josyf), Nalls, M.A. (Michael), Nauck, M. (Matthias), Neville, M.J. (Matthew), Nolte, I.M. (Ilja), Ong, K.K. (Ken K), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Pálsson, G. (Gunnar), Palmer, C.N.A. (Colin), Penninx, B.W.J.H., Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter P), Quintana-Murci, L. (Lluis), Räikkönen, K. (Katri), Ralhan, S. (Sarju), Rao, D.C. (Dabeeru C), Rheenen, W. (Wouter) van, Rich, S.S. (Stephen), Ridker, P.M. (Paul M), Rietveld, C.A. (Cornelius A), Robino, A. (Antonietta), Rooij, F.J.A. (Frank) van, Ruggiero, D., Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L.J. (Laura J), Scott, W.R. (William R), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), Setten, J. (Jessica) van, Sever, P.J. (Peter J), Sheu, W.H.-H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S.R. (Sharvari Rahul), Sigurdsson, J.K. (Jon K), Sikka, T.T. (Timo Tonis), Singh, J.R. (Jai Rup), Smith, B.H. (Blair), Stancáková, A. (Alena), Stanton, A. (Alice), Starr, J.M. (John), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M.A. (Morris A), Taylor, A.M. (Adele M), Taylor, K.D. (Kent), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R.P. (Russell), Tusié-Luna, T. (Teresa), Tzoulaki, I., Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J.H. (Jan), Vitart, V. (Veronique), Völker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S.M. (Salma M), Waldenberger, M. (Melanie), Wander, G.S. (Gurpreet S), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Wild, S.H. (Sarah), Yajnik, C.S. (Chittaranjan S), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F.W. (Folkert), Bakker, S.J.L. (Stephan), Becker, D.M. (Diane), Lehne, B. (Benjamin), Bennett, D.A. (David), Berg, L.H. (Leonard) van den, Berndt, S.I. (Sonja), Bharadwaj, D. (Dwaipayan), Bielak, L.F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Michael), Bouchard, C. (Claude), Bradfield, J.P. (Jonathan), Brody, J.A. (Jennifer A), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. (Mark), Cesarini, D. (David), Chambers, J.C. (John C), Chandak, G.R. (Giriraj), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Warrington, N.M. (Nicole), Cusi, D. (Daniele), Smith, G.D. (George Davey), Deary, I.J. (Ian J), Dorajoo, R. (Rajkumar), Duijn, C.M. (Cornelia) van, Ellinghaus, D. (David), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evangelou, E. (Evangelos), Evans, M.K. (Michele), Faul, J.D. (Jessica D), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S.F.A. (Struan), Griffiths, L.R. (Lyn R), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), Harst, P. (Pim) van der, Heng, C.K. (Chew-Kiat), Hicks, A.A. (Andrew A), Hochner, H., Huikuri, H.V. (Heikki), Hunt, S.C. (Steven), Jaddoe, V.W.V. (Vincent), De Jager, P., Johannesson, M. (Magnus), Johansson, A. (Åsa), Jonas, J.B. (Jost B), Jukema, J.W. (Jan Wouter), Junttila, M.J. (Juhani), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S.W. (Sander W), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R.A. (Rodney A), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N.G. (Nicholas), Ye, S. (Shu), Matullo, G., McCarthy, M.I. (Mark), Medland, S.E. (Sarah), Merriman, A., Metspalu, A. (Andres), Meyer, B.F. (Brian F), Mohlke, K.L. (Karen L), Montgomery, G.W. (Grant), Mook-Kanamori, D. (Dennis), Munroe, P. (Patricia), North, K.E. (Kari), Nyholt, D.R. (Dale), O’connell, J.R. (Jeffery R), Ober, C. (Carole), Oldehinkel, A.J. (Albertine), Palmas, W. (Walter), Pasterkamp, G.G. (Gerard G), Patin, E. (Etienne), Pennell, C.E. (Craig), Perusse, L. (Louis), Peyser, P.A. (Patricia A.), Pirastu, M. (Mario), Polderman, T.J.C. (Tinca), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Psaty, B.M. (Bruce M), Rioux, J.D. (John), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Sanghera, D.K. (Dharambir K), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M.B. (Matthias), Schunkert, H. (Heribert), Scott, R.A. (Robert), Shuldiner, A.R. (Alan R), Sim, X. (Xueling), Small, N. (Neil), Smith, J.A. (Jennifer A), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N.J. (Nicholas), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C.A. (Carol A), Weir, D.R. (David R), Whitfield, J. (John), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B.S. (Babette S.), Zonderman, A.B. (Alan B), Perola, M. (Markus), Magnusson, P.K. (Patrik), Uitterlinden, A.G. (André), Kooner, J.S. (Jaspal S.), Chasman, D.I. (Daniel), Loos, R.J.F. (Ruth), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. (Chris), Hayward, C. (Caroline), Walters, R.G. (Robin G), Perry, J.R.B. (John R. B.), Esko, T. (Tõnu), Helgason, A. (Agnar), Zwart, J-A. (John-Anker), Joshi, P.K. (Peter), Kubo, M. (Michiaki), Wilson, J.F. (James), Clark, D.W. (David W), Okada, Y. (Yukinori), Moore, K.H.S. (Kristjan H S), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C.L.K. (Catriona L K), Lin, K. (Kuang), Zhao, J.H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, M.C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T.M. (Traci M), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M.J. (Matthew J), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Dekker, A.M. (Annelot M), Eccles, D.A. (David A), Eijk, K.R. (Kristel) van, Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S.D. (Scott D.), de Haan, H.G. (Hugoline G), Harris, S.E. (Sarah), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. (Iris), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M.E. (Marcus), Li, S.A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M.E. (May E.), Most, P.J. (Peter) van der, Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R.B. (Rashmi B), Priyanka, T.D.S. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B.R. (Bishwa R), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M.C. (Melissa C), Smith, A.V. (Albert), Spek, A. (Ashley) van der, Spracklen, C.N. (Cassandra N), Strawbridge, R.J. (Rona), Tajuddin, S.M. (Salman M), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. (Helen), Wootton, R.E. (Robyn E), Yanek, L.R. (Lisa), Yao, J. (Jie), Yousri, N.A. (Noha A), Zhao, W. (Wei), Adeyemo, A.A. (Adebowale A), Afaq, S. (Saima), Aguilar-Salinas, C.A. (Carlos Alberto), Akiyama, M. (Masato), Albert, M.L. (Matthew L), Allison, M.A. (Matthew A), Alver, M. (Maris), Aung, T. (Tin), Azizi, J. (Joshan), Bentley, A.R. (Amy), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Borja, J.B. (Judith B), Borst, G.J. (Gert) de, Bottinger, E.P. (Erwin), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S.J. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y.-D.I. (Yii-Der I), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Concas, M.P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Dam, R.M. (Rob) van, Damulina, A. (Anna), Daneshpour, M.S. (Maryam S), Day, F.R. (Felix), Delgado, G., Dhana, K. (Klodian), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Doumatey, A. (Ayo), Dzimiri, N. (Nduna), Ebenesersdóttir, S.S. (S Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J.F. (Janine), Fischer, K. (Krista), Freedman, B.I. (Barry), Girotto, S., Goel, A. (Anuj), Gögele, M. (Martin), Goodarzi, M. (Mark), Graff, M.J. (Maud J.L.), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S.P. (Saskia P), Haiman, C.A. (Christopher), Halevy, A. (Avner), Harris, T.B. (Tamara B), Hedayati, M. (Mehdi), Heel, D.A. (David) van, Hirata, M. (Makoto), Höfer, I. (Imo), Hsiung, C.A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M.A. (Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N.D. (Nicola D), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C.C., Kleijn, D.P.V. (Dominique) de, Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Krämer, B.K. (Bernhard), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. (M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S.J. (Stephanie J), Loomis, S.J. (Stephanie J.), Lu, Y. (Yingchang), Luan, J. (Jian’an), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X.W. (Xue W), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I.Y. (Iona), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (P.), Moreno-Macías, H. (Hortensia), Mori, T.A. (Trevor A), Morrison, A.C. (Alanna), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A.D. (Alison D), Mutsert, R. (Reneé) de, Mychaleckyj, J.C. (Josyf), Nalls, M.A. (Michael), Nauck, M. (Matthias), Neville, M.J. (Matthew), Nolte, I.M. (Ilja), Ong, K.K. (Ken K), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Pálsson, G. (Gunnar), Palmer, C.N.A. (Colin), Penninx, B.W.J.H., Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter P), Quintana-Murci, L. (Lluis), Räikkönen, K. (Katri), Ralhan, S. (Sarju), Rao, D.C. (Dabeeru C), Rheenen, W. (Wouter) van, Rich, S.S. (Stephen), Ridker, P.M. (Paul M), Rietveld, C.A. (Cornelius A), Robino, A. (Antonietta), Rooij, F.J.A. (Frank) van, Ruggiero, D., Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L.J. (Laura J), Scott, W.R. (William R), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), Setten, J. (Jessica) van, Sever, P.J. (Peter J), Sheu, W.H.-H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S.R. (Sharvari Rahul), Sigurdsson, J.K. (Jon K), Sikka, T.T. (Timo Tonis), Singh, J.R. (Jai Rup), Smith, B.H. (Blair), Stancáková, A. (Alena), Stanton, A. (Alice), Starr, J.M. (John), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M.A. (Morris A), Taylor, A.M. (Adele M), Taylor, K.D. (Kent), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R.P. (Russell), Tusié-Luna, T. (Teresa), Tzoulaki, I., Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J.H. (Jan), Vitart, V. (Veronique), Völker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S.M. (Salma M), Waldenberger, M. (Melanie), Wander, G.S. (Gurpreet S), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Wild, S.H. (Sarah), Yajnik, C.S. (Chittaranjan S), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F.W. (Folkert), Bakker, S.J.L. (Stephan), Becker, D.M. (Diane), Lehne, B. (Benjamin), Bennett, D.A. (David), Berg, L.H. (Leonard) van den, Berndt, S.I. (Sonja), Bharadwaj, D. (Dwaipayan), Bielak, L.F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Michael), Bouchard, C. (Claude), Bradfield, J.P. (Jonathan), Brody, J.A. (Jennifer A), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. (Mark), Cesarini, D. (David), Chambers, J.C. (John C), Chandak, G.R. (Giriraj), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Warrington, N.M. (Nicole), Cusi, D. (Daniele), Smith, G.D. (George Davey), Deary, I.J. (Ian J), Dorajoo, R. (Rajkumar), Duijn, C.M. (Cornelia) van, Ellinghaus, D. (David), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evangelou, E. (Evangelos), Evans, M.K. (Michele), Faul, J.D. (Jessica D), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S.F.A. (Struan), Griffiths, L.R. (Lyn R), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), Harst, P. (Pim) van der, Heng, C.K. (Chew-Kiat), Hicks, A.A. (Andrew A), Hochner, H., Huikuri, H.V. (Heikki), Hunt, S.C. (Steven), Jaddoe, V.W.V. (Vincent), De Jager, P., Johannesson, M. (Magnus), Johansson, A. (Åsa), Jonas, J.B. (Jost B), Jukema, J.W. (Jan Wouter), Junttila, M.J. (Juhani), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S.W. (Sander W), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R.A. (Rodney A), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N.G. (Nicholas), Ye, S. (Shu), Matullo, G., McCarthy, M.I. (Mark), Medland, S.E. (Sarah), Merriman, A., Metspalu, A. (Andres), Meyer, B.F. (Brian F), Mohlke, K.L. (Karen L), Montgomery, G.W. (Grant), Mook-Kanamori, D. (Dennis), Munroe, P. (Patricia), North, K.E. (Kari), Nyholt, D.R. (Dale), O’connell, J.R. (Jeffery R), Ober, C. (Carole), Oldehinkel, A.J. (Albertine), Palmas, W. (Walter), Pasterkamp, G.G. (Gerard G), Patin, E. (Etienne), Pennell, C.E. (Craig), Perusse, L. (Louis), Peyser, P.A. (Patricia A.), Pirastu, M. (Mario), Polderman, T.J.C. (Tinca), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Psaty, B.M. (Bruce M), Rioux, J.D. (John), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Sanghera, D.K. (Dharambir K), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M.B. (Matthias), Schunkert, H. (Heribert), Scott, R.A. (Robert), Shuldiner, A.R. (Alan R), Sim, X. (Xueling), Small, N. (Neil), Smith, J.A. (Jennifer A), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N.J. (Nicholas), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C.A. (Carol A), Weir, D.R. (David R), Whitfield, J. (John), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B.S. (Babette S.), Zonderman, A.B. (Alan B), Perola, M. (Markus), Magnusson, P.K. (Patrik), Uitterlinden, A.G. (André), Kooner, J.S. (Jaspal S.), Chasman, D.I. (Daniel), Loos, R.J.F. (Ruth), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. (Chris), Hayward, C. (Caroline), Walters, R.G. (Robin G), Perry, J.R.B. (John R. B.), Esko, T. (Tõnu), Helgason, A. (Agnar), Zwart, J-A. (John-Anker), Joshi, P.K. (Peter), Kubo, M. (Michiaki), and Wilson, J.F. (James)

Abstract

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.

Published
2019
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25. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author

Vries, P.S. (Paul) de, Brown, M.R., Bentley, A.R. (Amy), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Schwander, K., Kraja, A. (Aldi), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Huffman, J.E. (Jennifer E.), Musani, S.K. (Solomon K.), Li, C. (Changwei), Feitosa, M.F. (Mary Furlan), Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Deng, X. (Xuan), Dorajoo, R. (Rajkumar), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Evangelou, E. (Evangelos), Graff, M.J. (Maud J.L.), Alver, M. (Maris), Boissel, M. (Mathilde), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gandin, I. (Ilaria), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), Hartwig, F.P. (Fernando P.), He, M. (Meian), Horimoto, A.R.V.R. (Andrea R V R), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Lee, J.H. (Joseph H.), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Matoba, N. (Nana), Nolte, I.M. (Ilja), Pietzner, M. (Maik), Riaz, M. (Muhammad), Said, M.A. (M Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Ballantyne, C. (Christie), Boerwinkle, E.A. (Eric), Broeckel, U. (Ulrich), Campbell, A. (Archie), Canouil, M. (Mickaël), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J. (John), Faire, U. (Ulf) de, de Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, de Silva, H.J. (H Janaka), Ding, J. (Jingzhong), Dominiczak, A.F. (Anna F.), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Eppinga, R.N. (Ruben N.), Faul, J.D. (Jessica D.), Fisher, V. (Virginia), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Ghanbari, M. (Mohsen), Giulianini, F. (Franco), Grabe, H.J. (Hans Jörgen), Grove, M.L. (Megan), Gu, C. (Charles), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Hixson, J.E. (James E.), Howard, B.V. (Barbara V.), Ikram, M.A. (Arfan), Jacobs, D.R. (David R.), Johnson, C. (Craig), Jonas, J.B., Kammerer, C.M. (Candace), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas O.), Koh, W.-P. (Woon-Puay), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kooperberg, C. (Charles), Krieger, J.E. (José), Kritchevsky, S.B. (Steve B.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lemaitre, R.N. (Rozenn ), Li, Y. (Yize), Liang, J. (Jingjing), Liu, J. (Jianjun), Liu, K. (Kiang), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W.), McKenzie, C.A. (Colin A.), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen L.), Mosley, T.H. (Thomas H.), Mukamal, K. (Kenneth), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), O´Connell, J.R., Palmer, N.D. (Nicholette), Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Reiner, A.P. (Alex P.), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Robino, A. (Antonietta), Robinson, J.G. (Jennifer), Rose, L.M. (Lynda M.), Rudan, I. (Igor), Schmidt, C.O. (Carsten O.), Schreiner, P.J. (Pamela), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Tan, N. (Nicholas), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Uitterlinden, A.G. (André), Heemst, D. (Diana) van, Vuckovic, D. (Dragana), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y. (Yujie), Wang, Z. (Zhe), Wei, W.B. (Wen Bin), Williams, C. (Christine), Wilson, G. (Gregory), Wojczynski, M.K. (Mary ), Yao, J. (Jie), Yu, B. (Bing), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Horta, B.L. (Bernardo L.), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Laakso, M. (Markku), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Penninx, B.W.J.H. (Brenda), Pereira, A.C. (Alexandre C.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Harst, P. (Pim) van der, Wagenknecht, L.E. (Lynne), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda R.), Zheng, W. (Wei), Elliott, P. (Paul), North, K.E. (Kari), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Liu, C.-T. (Ching-Ti), Liu, Y. (YongMei), Psaty, B.M. (Bruce M.), Jarvelin, M.-R. (Marjo-Riitta), Dam, R.M. (Rob) van, Kardia, S.L.R. (Sharon), Dominiczak, A. (Anna), Rotimi, C. (Charles), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin R.), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (Shyong), Wong, T.Y. (Tien Yin), Liu, J. (Jingmin), Rotter, J.I. (Jerome I.), Gauderman, W.J. (W James), Province, M.A. (Michael A.), Munroe, P. (Patricia), Rice, K. (Kenneth), Chasman, D.I. (Daniel), Cupples, L.A. (L Adrienne), Tobin, M.D. (Martin), Morrison, A.C. (Alanna), Vries, P.S. (Paul) de, Brown, M.R., Bentley, A.R. (Amy), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Schwander, K., Kraja, A. (Aldi), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Huffman, J.E. (Jennifer E.), Musani, S.K. (Solomon K.), Li, C. (Changwei), Feitosa, M.F. (Mary Furlan), Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Deng, X. (Xuan), Dorajoo, R. (Rajkumar), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Evangelou, E. (Evangelos), Graff, M.J. (Maud J.L.), Alver, M. (Maris), Boissel, M. (Mathilde), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gandin, I. (Ilaria), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), Hartwig, F.P. (Fernando P.), He, M. (Meian), Horimoto, A.R.V.R. (Andrea R V R), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Lee, J.H. (Joseph H.), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Matoba, N. (Nana), Nolte, I.M. (Ilja), Pietzner, M. (Maik), Riaz, M. (Muhammad), Said, M.A. (M Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Ballantyne, C. (Christie), Boerwinkle, E.A. (Eric), Broeckel, U. (Ulrich), Campbell, A. (Archie), Canouil, M. (Mickaël), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J. (John), Faire, U. (Ulf) de, de Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, de Silva, H.J. (H Janaka), Ding, J. (Jingzhong), Dominiczak, A.F. (Anna F.), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Eppinga, R.N. (Ruben N.), Faul, J.D. (Jessica D.), Fisher, V. (Virginia), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Ghanbari, M. (Mohsen), Giulianini, F. (Franco), Grabe, H.J. (Hans Jörgen), Grove, M.L. (Megan), Gu, C. (Charles), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Hixson, J.E. (James E.), Howard, B.V. (Barbara V.), Ikram, M.A. (Arfan), Jacobs, D.R. (David R.), Johnson, C. (Craig), Jonas, J.B., Kammerer, C.M. (Candace), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas O.), Koh, W.-P. (Woon-Puay), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kooperberg, C. (Charles), Krieger, J.E. (José), Kritchevsky, S.B. (Steve B.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lemaitre, R.N. (Rozenn ), Li, Y. (Yize), Liang, J. (Jingjing), Liu, J. (Jianjun), Liu, K. (Kiang), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W.), McKenzie, C.A. (Colin A.), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen L.), Mosley, T.H. (Thomas H.), Mukamal, K. (Kenneth), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), O´Connell, J.R., Palmer, N.D. (Nicholette), Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Reiner, A.P. (Alex P.), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Robino, A. (Antonietta), Robinson, J.G. (Jennifer), Rose, L.M. (Lynda M.), Rudan, I. (Igor), Schmidt, C.O. (Carsten O.), Schreiner, P.J. (Pamela), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Tan, N. (Nicholas), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Uitterlinden, A.G. (André), Heemst, D. (Diana) van, Vuckovic, D. (Dragana), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y. (Yujie), Wang, Z. (Zhe), Wei, W.B. (Wen Bin), Williams, C. (Christine), Wilson, G. (Gregory), Wojczynski, M.K. (Mary ), Yao, J. (Jie), Yu, B. (Bing), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Horta, B.L. (Bernardo L.), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Laakso, M. (Markku), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Penninx, B.W.J.H. (Brenda), Pereira, A.C. (Alexandre C.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Harst, P. (Pim) van der, Wagenknecht, L.E. (Lynne), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda R.), Zheng, W. (Wei), Elliott, P. (Paul), North, K.E. (Kari), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Liu, C.-T. (Ching-Ti), Liu, Y. (YongMei), Psaty, B.M. (Bruce M.), Jarvelin, M.-R. (Marjo-Riitta), Dam, R.M. (Rob) van, Kardia, S.L.R. (Sharon), Dominiczak, A. (Anna), Rotimi, C. (Charles), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin R.), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (Shyong), Wong, T.Y. (Tien Yin), Liu, J. (Jingmin), Rotter, J.I. (Jerome I.), Gauderman, W.J. (W James), Province, M.A. (Michael A.), Munroe, P. (Patricia), Rice, K. (Kenneth), Chasman, D.I. (Daniel), Cupples, L.A. (L Adrienne), Tobin, M.D. (Martin), and Morrison, A.C. (Alanna)

Abstract

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

Published
2019
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26. Associations of autozygosity with a broad range of human phenotypes

Author

Clark, D. W. (David W.), Okada, Y. (Yukinori), Moore, K. H. (Kristjan H. S.), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C. L. (Catriona L. K.), Lin, K. (Kuang), Zhao, J. H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T. M. (Traci M.), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M. J. (Matthew J.), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D. L. (Diana L.), Dekker, A. M. (Annelot M.), Eccles, D. A. (David A.), Van Eijk, K. R. (Kristel R.), Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S. D. (Scott D.), de Haan, H. G. (Hugoline G.), Harris, S. E. (Sarah E.), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. E. (Iris E.), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M. E. (Marcus E.), Li, S. A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M. E. (May E.), van der Most, P. J. (Peter J.), Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R. B. (Rashmi B.), Priyanka, T. D. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B. R. (Bishwa R.), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M. C. (Melissa C.), Smith, A. V. (Albert Vernon), van der Spek, A. (Ashley), Spracklen, C. N. (Cassandra N.), Strawbridge, R. J. (Rona J.), Tajuddin, S. M. (Salman M.), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. R. (Helen R.), Wootton, R. E. (Robyn E.), Yanek, L. R. (Lisa R.), Yao, J. (Jie), Yousri, N. A. (Noha A.), Zhao, W. (Wei), Adeyemo, A. A. (Adebowale A.), Afaq, S. (Saima), Alberto Aguilar-Salinas, C. (Carlos), Akiyama, M. (Masato), Albert, M. L. (Matthew L.), Allison, M. A. (Matthew A.), Alver, M. (Maris), Aung, T. (Tin), Azizi, F. (Fereidoun), Bentley, A. R. (Amy R.), Boeing, H. (Heiner), Boerwinkle, E. (Eric), Borja, J. B. (Judith B.), de Borst, G. J. (Gert J.), Bottinger, E. P. (Erwin P.), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y. I. (Yii-Der I.), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F. S. (Francis S.), Concas, M. P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Van Dam, R. M. (Rob M.), Damulina, A. (Anna), Daneshpour, M. S. (Maryam S.), Day, F. R. (Felix R.), Delgado, G. E. (Graciela E.), Dhana, K. (Klodian), Doney, A. S. (Alexander S. F.), Doerr, M. (Marcus), Doumatey, A. P. (Ayo P.), Dzimiri, N. (Nduna), Ebenesersdottir, S. S. (S. Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J. F. (Janine F.), Fischer, K. (Krista), Freedman, B. I. (Barry I.), Girotto, G. (Giorgia), Goel, A. (Anuj), Gogele, M. (Martin), Goodarzi, M. O. (Mark O.), Graff, M. (Mariaelisa), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D. F. (Daniel F.), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S. P. (Saskia P.), Haiman, C. A. (Christopher A.), Halevy, A. (Avner), Harris, T. B. (Tamara B.), Hedayati, M. (Mehdi), van Heel, D. A. (David A.), Hirata, M. (Makoto), Hofer, I. (Imo), Hsiung, C. A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M. A. (M. Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N. D. (Nicola D.), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C. C. (Chiea Chuen), de Kleijn, D. P. (Dominique P. V.), Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Kramer, B. K. (Bernhard K.), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Lawlor, D. A. (Deborah A.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. M. (Markus M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S. J. (Stephanie J.), Loomis, S. (Stephanie), Lu, Y. (Yingchang), Luan, J. (Jian'an), Magi, R. (Reedik), Manichaikul, A. W. (Ani W.), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X. W. (Xue W.), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I. Y. (Iona Y.), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (Pierre-Emmanuel), Moreno-Macias, H. (Hortensia), Mori, T. A. (Trevor A.), Morrison, A. C. (Alanna C.), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A. D. (Alison D.), de Mutsert, R. (Renee), Mychaleckyj, J. C. (Josyf C.), Nalls, M. A. (Mike A.), Nauck, M. (Matthias), Neville, M. J. (Matt J.), Nolte, I. M. (Ilja M.), Ong, K. K. (Ken K.), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Palsson, G. (Gunnar), Pankow, J. S. (James S.), Pattaro, C. (Cristian), Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Quintana-Murci, L. (Lluis), Raikkonen, K. (Katri), Ralhan, S. (Sarju), Rao, D. C. (Dabeeru C.), van Rheenen, W. (Wouter), Rich, S. S. (Stephen S.), Ridker, P. M. (Paul M.), Rietveld, C. A. (Cornelius A.), Robino, A. (Antonietta), van Rooij, F. J. (Frank J. A.), Ruggiero, D. (Daniela), Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Felicita Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L. J. (Laura J.), Scott, W. R. (William R.), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), van Setten, J. (Jessica), Sever, P. J. (Peter J.), Sheu, W. H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S. R. (Sharvari Rahul), Sigurdsson, J. K. (Jon K.), Sikka, T. T. (Timo Tonis), Singh, J. R. (Jai Rup), Smith, B. H. (Blair H.), Stancakova, A. (Alena), Stanton, A. (Alice), Starr, J. M. (John M.), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M. A. (Morris A.), Taylor, A. M. (Adele M.), Taylor, K. D. (Kent D.), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R. P. (Russell P.), Tusie-Luna, T. (Teresa), Tzoulaki, I. (Ioanna), Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J. H. (Jan H.), Vitart, V. (Veronique), Volker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S. M. (Salma M.), Waldenberger, M. (Melanie), Wander, G. S. (Gurpreet S.), Wang, Y. X. (Ya Xing), Wareham, N. J. (Nicholas J.), Wild, S. (Sarah), Yajnik, C. S. (Chittaranjan S.), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F. W. (Folkert W.), Bakker, S. J. (Stephan J. L.), Becker, D. M. (Diane M.), Lehne, B. (Benjamin), Bennett, D. A. (David A.), van den Berg, L. H. (Leonard H.), Berndt, S. I. (Sonja I.), Bharadwaj, D. (Dwaipayan), Bielak, L. F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Mike), Bouchard, C. (Claude), Bradfield, J. P. (Jonathan P.), Brody, J. A. (Jennifer A.), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. J. (Mark J.), Cesarini, D. (David), Chambers, J. C. (John C.), Chandak, G. R. (Giriraj Ratan), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Cornelis, M. (Marilyn), Cusi, D. (Daniele), Smith, G. D. (George Davey), Deary, I. J. (Ian J.), Dorajoo, R. (Rajkumar), van Duijn, C. M. (Cornelia M.), Ellinghaus, D. (David), Erdmann, J. (Jeanette), Eriksson, J. G. (Johan G.), Evangelou, E. (Evangelos), Evans, M. K. (Michele K.), Faul, J. D. (Jessica D.), Feenstra, B. (Bjarke), Feitosa, M. (Mary), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S. F. (Struan F. A.), Griffiths, L. R. (Lyn R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), van der Harst, P. (Pim), Heng, C.-K. (Chew-Kiat), Hicks, A. A. (Andrew A.), Hochner, H. (Hagit), Huikuri, H. (Heikki), Hunt, S. C. (Steven C.), Jaddoe, V. W. (Vincent W. V.), De Jager, P. L. (Philip L.), Johannesson, M. (Magnus), Johansson, A. (Asa), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Junttila, J. (Juhani), Kaprio, J. (Jaakko), Kardia, S. L. (Sharon L. R.), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S. W. (Sander W.), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R. A. (Rodney A.), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N. G. (Nicholas G.), Marz, W. (Winfried), Matullo, G. (Giuseppe), McCarthy, M. I. (Mark I.), Medland, S. E. (Sarah E.), Merriman, T. R. (Tony R.), Metspalu, A. (Andres), Meyer, B. F. (Brian F.), Mohlke, K. L. (Karen L.), Montgomery, G. W. (Grant W.), Mook-Kanamori, D. (Dennis), Munroe, P. B. (Patricia B.), North, K. E. (Kari E.), Nyholt, D. R. (Dale R.), O'connell, J. R. (Jeffery R.), Ober, C. (Carole), Oldehinkel, A. J. (Albertine J.), Palmas, W. (Walter), Palmer, C. (Colin), Pasterkamp, G. G. (Gerard G.), Patin, E. (Etienne), Pennell, C. E. (Craig E.), Perusse, L. (Louis), Peyser, P. A. (Patricia A.), Pirastu, M. (Mario), Polderman, T. J. (Tinca J. C.), Porteous, D. J. (David J.), Posthuma, D. (Danielle), Psaty, B. M. (Bruce M.), Rioux, J. D. (John D.), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J. I. (Jerome I.), Rudan, I. (Igor), Den Ruijter, H. M. (Hester M.), Sanghera, D. K. (Dharambir K.), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M. B. (Matthias B.), Schunkert, H. (Heribert), Scott, R. A. (Robert A.), Shuldiner, A. R. (Alan R.), Sim, X. (Xueling), Small, N. (Neil), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N. J. (Nicholas J.), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C. A. (Carol A.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B. S. (Babette S.), Zonderman, A. B. (Alan B.), Perola, M. (Markus), Magnusson, P. K. (Patrik K. E.), Uitterlinden, A. G. (Andre G.), Kooner, J. S. (Jaspal S.), Chasman, D. I. (Daniel I.), Loos, R. J. (Ruth J. F.), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. S. (Chris S.), Hayward, C. (Caroline), Walters, R. G. (Robin G.), Perry, J. R. (John R. B.), Esko, T. (Tonu), Helgason, A. (Agnar), Stefansson, K. (Kari), Joshi, P. K. (Peter K.), Kubo, M. (Michiaki), Wilson, J. F. (James F.), Clark, D. W. (David W.), Okada, Y. (Yukinori), Moore, K. H. (Kristjan H. S.), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C. L. (Catriona L. K.), Lin, K. (Kuang), Zhao, J. H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T. M. (Traci M.), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M. J. (Matthew J.), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D. L. (Diana L.), Dekker, A. M. (Annelot M.), Eccles, D. A. (David A.), Van Eijk, K. R. (Kristel R.), Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S. D. (Scott D.), de Haan, H. G. (Hugoline G.), Harris, S. E. (Sarah E.), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. E. (Iris E.), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M. E. (Marcus E.), Li, S. A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M. E. (May E.), van der Most, P. J. (Peter J.), Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R. B. (Rashmi B.), Priyanka, T. D. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B. R. (Bishwa R.), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M. C. (Melissa C.), Smith, A. V. (Albert Vernon), van der Spek, A. (Ashley), Spracklen, C. N. (Cassandra N.), Strawbridge, R. J. (Rona J.), Tajuddin, S. M. (Salman M.), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. R. (Helen R.), Wootton, R. E. (Robyn E.), Yanek, L. R. (Lisa R.), Yao, J. (Jie), Yousri, N. A. (Noha A.), Zhao, W. (Wei), Adeyemo, A. A. (Adebowale A.), Afaq, S. (Saima), Alberto Aguilar-Salinas, C. (Carlos), Akiyama, M. (Masato), Albert, M. L. (Matthew L.), Allison, M. A. (Matthew A.), Alver, M. (Maris), Aung, T. (Tin), Azizi, F. (Fereidoun), Bentley, A. R. (Amy R.), Boeing, H. (Heiner), Boerwinkle, E. (Eric), Borja, J. B. (Judith B.), de Borst, G. J. (Gert J.), Bottinger, E. P. (Erwin P.), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y. I. (Yii-Der I.), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F. S. (Francis S.), Concas, M. P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Van Dam, R. M. (Rob M.), Damulina, A. (Anna), Daneshpour, M. S. (Maryam S.), Day, F. R. (Felix R.), Delgado, G. E. (Graciela E.), Dhana, K. (Klodian), Doney, A. S. (Alexander S. F.), Doerr, M. (Marcus), Doumatey, A. P. (Ayo P.), Dzimiri, N. (Nduna), Ebenesersdottir, S. S. (S. Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J. F. (Janine F.), Fischer, K. (Krista), Freedman, B. I. (Barry I.), Girotto, G. (Giorgia), Goel, A. (Anuj), Gogele, M. (Martin), Goodarzi, M. O. (Mark O.), Graff, M. (Mariaelisa), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D. F. (Daniel F.), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S. P. (Saskia P.), Haiman, C. A. (Christopher A.), Halevy, A. (Avner), Harris, T. B. (Tamara B.), Hedayati, M. (Mehdi), van Heel, D. A. (David A.), Hirata, M. (Makoto), Hofer, I. (Imo), Hsiung, C. A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M. A. (M. Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N. D. (Nicola D.), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C. C. (Chiea Chuen), de Kleijn, D. P. (Dominique P. V.), Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Kramer, B. K. (Bernhard K.), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Lawlor, D. A. (Deborah A.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. M. (Markus M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S. J. (Stephanie J.), Loomis, S. (Stephanie), Lu, Y. (Yingchang), Luan, J. (Jian'an), Magi, R. (Reedik), Manichaikul, A. W. (Ani W.), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X. W. (Xue W.), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I. Y. (Iona Y.), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (Pierre-Emmanuel), Moreno-Macias, H. (Hortensia), Mori, T. A. (Trevor A.), Morrison, A. C. (Alanna C.), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A. D. (Alison D.), de Mutsert, R. (Renee), Mychaleckyj, J. C. (Josyf C.), Nalls, M. A. (Mike A.), Nauck, M. (Matthias), Neville, M. J. (Matt J.), Nolte, I. M. (Ilja M.), Ong, K. K. (Ken K.), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Palsson, G. (Gunnar), Pankow, J. S. (James S.), Pattaro, C. (Cristian), Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Quintana-Murci, L. (Lluis), Raikkonen, K. (Katri), Ralhan, S. (Sarju), Rao, D. C. (Dabeeru C.), van Rheenen, W. (Wouter), Rich, S. S. (Stephen S.), Ridker, P. M. (Paul M.), Rietveld, C. A. (Cornelius A.), Robino, A. (Antonietta), van Rooij, F. J. (Frank J. A.), Ruggiero, D. (Daniela), Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Felicita Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L. J. (Laura J.), Scott, W. R. (William R.), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), van Setten, J. (Jessica), Sever, P. J. (Peter J.), Sheu, W. H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S. R. (Sharvari Rahul), Sigurdsson, J. K. (Jon K.), Sikka, T. T. (Timo Tonis), Singh, J. R. (Jai Rup), Smith, B. H. (Blair H.), Stancakova, A. (Alena), Stanton, A. (Alice), Starr, J. M. (John M.), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M. A. (Morris A.), Taylor, A. M. (Adele M.), Taylor, K. D. (Kent D.), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R. P. (Russell P.), Tusie-Luna, T. (Teresa), Tzoulaki, I. (Ioanna), Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J. H. (Jan H.), Vitart, V. (Veronique), Volker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S. M. (Salma M.), Waldenberger, M. (Melanie), Wander, G. S. (Gurpreet S.), Wang, Y. X. (Ya Xing), Wareham, N. J. (Nicholas J.), Wild, S. (Sarah), Yajnik, C. S. (Chittaranjan S.), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F. W. (Folkert W.), Bakker, S. J. (Stephan J. L.), Becker, D. M. (Diane M.), Lehne, B. (Benjamin), Bennett, D. A. (David A.), van den Berg, L. H. (Leonard H.), Berndt, S. I. (Sonja I.), Bharadwaj, D. (Dwaipayan), Bielak, L. F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Mike), Bouchard, C. (Claude), Bradfield, J. P. (Jonathan P.), Brody, J. A. (Jennifer A.), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. J. (Mark J.), Cesarini, D. (David), Chambers, J. C. (John C.), Chandak, G. R. (Giriraj Ratan), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Cornelis, M. (Marilyn), Cusi, D. (Daniele), Smith, G. D. (George Davey), Deary, I. J. (Ian J.), Dorajoo, R. (Rajkumar), van Duijn, C. M. (Cornelia M.), Ellinghaus, D. (David), Erdmann, J. (Jeanette), Eriksson, J. G. (Johan G.), Evangelou, E. (Evangelos), Evans, M. K. (Michele K.), Faul, J. D. (Jessica D.), Feenstra, B. (Bjarke), Feitosa, M. (Mary), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S. F. (Struan F. A.), Griffiths, L. R. (Lyn R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), van der Harst, P. (Pim), Heng, C.-K. (Chew-Kiat), Hicks, A. A. (Andrew A.), Hochner, H. (Hagit), Huikuri, H. (Heikki), Hunt, S. C. (Steven C.), Jaddoe, V. W. (Vincent W. V.), De Jager, P. L. (Philip L.), Johannesson, M. (Magnus), Johansson, A. (Asa), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Junttila, J. (Juhani), Kaprio, J. (Jaakko), Kardia, S. L. (Sharon L. R.), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S. W. (Sander W.), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R. A. (Rodney A.), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N. G. (Nicholas G.), Marz, W. (Winfried), Matullo, G. (Giuseppe), McCarthy, M. I. (Mark I.), Medland, S. E. (Sarah E.), Merriman, T. R. (Tony R.), Metspalu, A. (Andres), Meyer, B. F. (Brian F.), Mohlke, K. L. (Karen L.), Montgomery, G. W. (Grant W.), Mook-Kanamori, D. (Dennis), Munroe, P. B. (Patricia B.), North, K. E. (Kari E.), Nyholt, D. R. (Dale R.), O'connell, J. R. (Jeffery R.), Ober, C. (Carole), Oldehinkel, A. J. (Albertine J.), Palmas, W. (Walter), Palmer, C. (Colin), Pasterkamp, G. G. (Gerard G.), Patin, E. (Etienne), Pennell, C. E. (Craig E.), Perusse, L. (Louis), Peyser, P. A. (Patricia A.), Pirastu, M. (Mario), Polderman, T. J. (Tinca J. C.), Porteous, D. J. (David J.), Posthuma, D. (Danielle), Psaty, B. M. (Bruce M.), Rioux, J. D. (John D.), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J. I. (Jerome I.), Rudan, I. (Igor), Den Ruijter, H. M. (Hester M.), Sanghera, D. K. (Dharambir K.), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M. B. (Matthias B.), Schunkert, H. (Heribert), Scott, R. A. (Robert A.), Shuldiner, A. R. (Alan R.), Sim, X. (Xueling), Small, N. (Neil), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N. J. (Nicholas J.), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C. A. (Carol A.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B. S. (Babette S.), Zonderman, A. B. (Alan B.), Perola, M. (Markus), Magnusson, P. K. (Patrik K. E.), Uitterlinden, A. G. (Andre G.), Kooner, J. S. (Jaspal S.), Chasman, D. I. (Daniel I.), Loos, R. J. (Ruth J. F.), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. S. (Chris S.), Hayward, C. (Caroline), Walters, R. G. (Robin G.), Perry, J. R. (John R. B.), Esko, T. (Tonu), Helgason, A. (Agnar), Stefansson, K. (Kari), Joshi, P. K. (Peter K.), Kubo, M. (Michiaki), and Wilson, J. F. (James F.)

Abstract

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.

Published
2019

27. Associations of autozygosity with a broad range of human phenotypes

Author

Clark, D.W., Okada, Y., Moore, K.H.S., Mason, D., Pirastu, N., Gandin, I., Mattsson, H., Barnes, C.L.K., Lin, K., Zhao, J.H., Deelen, P., Rohde, R., Schurmann, C., Guo, X., Giulianini, F., Zhang, W., Medina-Gomez, C., Karlsson, R., Bao, Y., Bartz, T.M., Baumbach, C., Biino, G., Bixley, M.J., Brumat, M., Chai, J.F., Corre, T., Cousminer, D.L., Dekker, A.M., Eccles, D.A., van Eijk, K.R., Fuchsberger, C., Gao, H., Germain, M., Gordon, S.D., de Haan, H.G., Harris, S.E., Hofer, E., Huerta-Chagoya, A., Igartua, C., Jansen, I.E., Jia, Y., Kacprowski, T., Karlsson, T., Kleber, M.E., Li, S.A., Li-Gao, R., Mahajan, A., Matsuda, K., Meidtner, K., Meng, W., Montasser, M.E., van der Most, P.J., Munz, M., Nutile, T., Palviainen, T., Prasad, G., Prasad, R.B., Priyanka, T.D.S., Rizzi, F., Salvi, E., Sapkota, B.R., Shriner, D., Skotte, L., Smart, M.C., Smith, A.V., van der Spek, A., Spracklen, C.N., Strawbridge, R.J., Tajuddin, S.M., Trompet, S., Turman, C., Verweij, N., Viberti, C., Wang, L., Warren, H.R., Wootton, R.E., Yanek, L.R., Yao, J., Yousri, N.A., Zhao, W., Adeyemo, A.A., Afaq, S., Aguilar-Salinas, C.A., Akiyama, M., Albert, M.L., Allison, M.A., Alver, M., Aung, T., Azizi, F., Bentley, A.R., Boeing, H., Boerwinkle, E., Borja, J.B., de Borst, G.J., Bottinger, E.P., Broer, L., Campbell, H., Chanock, S., Chee, M.L., Chen, G., Clark, D.W., Okada, Y., Moore, K.H.S., Mason, D., Pirastu, N., Gandin, I., Mattsson, H., Barnes, C.L.K., Lin, K., Zhao, J.H., Deelen, P., Rohde, R., Schurmann, C., Guo, X., Giulianini, F., Zhang, W., Medina-Gomez, C., Karlsson, R., Bao, Y., Bartz, T.M., Baumbach, C., Biino, G., Bixley, M.J., Brumat, M., Chai, J.F., Corre, T., Cousminer, D.L., Dekker, A.M., Eccles, D.A., van Eijk, K.R., Fuchsberger, C., Gao, H., Germain, M., Gordon, S.D., de Haan, H.G., Harris, S.E., Hofer, E., Huerta-Chagoya, A., Igartua, C., Jansen, I.E., Jia, Y., Kacprowski, T., Karlsson, T., Kleber, M.E., Li, S.A., Li-Gao, R., Mahajan, A., Matsuda, K., Meidtner, K., Meng, W., Montasser, M.E., van der Most, P.J., Munz, M., Nutile, T., Palviainen, T., Prasad, G., Prasad, R.B., Priyanka, T.D.S., Rizzi, F., Salvi, E., Sapkota, B.R., Shriner, D., Skotte, L., Smart, M.C., Smith, A.V., van der Spek, A., Spracklen, C.N., Strawbridge, R.J., Tajuddin, S.M., Trompet, S., Turman, C., Verweij, N., Viberti, C., Wang, L., Warren, H.R., Wootton, R.E., Yanek, L.R., Yao, J., Yousri, N.A., Zhao, W., Adeyemo, A.A., Afaq, S., Aguilar-Salinas, C.A., Akiyama, M., Albert, M.L., Allison, M.A., Alver, M., Aung, T., Azizi, F., Bentley, A.R., Boeing, H., Boerwinkle, E., Borja, J.B., de Borst, G.J., Bottinger, E.P., Broer, L., Campbell, H., Chanock, S., Chee, M.L., and Chen, G.

Abstract

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.

Published
2019

28. List of contributors

Author

Adesina, Adeyemi, Ali, Ernie Suzana, Al-Maharma, Ahmad Y., Amith Kumar, S.J., Aquino, Marcos, Azad, Muhammad Muzammil, Balaji, D., Bharath, K.N., Bhuvaneswari, V., Binoj, B.S., Bishi, Dillip Kumar, Bufalino, Lina, Burela, Ramesh Gupta, Chaturvedi, Adarsh, Chaudhary, Vijay, Costa, Lívia Ribeiro, Das, Partha Pratim, Denzin Tonoli, Gustavo Henrique, Dileepkumar, S.G., dos Santos, Sergio Francisco, Ejaz, Mohsin, Ezhilarasu, Hariharan, Gangil, Brijesh, Genc, Garip, Gisip, Judith, Gopal, P.M., Gorbatyuk, Sergey, Gupta, Manan, Gupta, Raju Kumar, Hein, Paulo Ricardo Gherardi, Hwang, Soo-Kyung, Indran, S., Iqbal, Mohammad Irfan, Isanaka, Bhargav Reddy, Jafrey Daniel James, D., Jain, Akshat, Jayanarayanan, K., Kamineni, Jagath Narayana, Kamperidou, V., Kamran Afaq, S., Kavimani, V., Kim, Hyun Joong, Koc, Busra, Koltsou, P., Kong, Ing, Konstandinidis, A., Koruk, Hasan, Kushvaha, Vinod, Madhu, P., Manicoba, Ernesto, Manjunatha, G.B., Manoharan, S., Markert, Bernd, Mathapati, Santosh S., Mazumder, Nur-Us-Shafa, Mini, K.M., Mizan, Rashed Al, Muhammad, Siti Nuramirah Rabbani, Navaneethakrishnan, Palanisamy, Padhi, Priyadarshini, Papadopoulos, S., Patil, Sandeep P., Prateek, Praveenkumara, J., Rahim, Mohd Hasbi Ab., Rajendran, Rejeesh C., Rajeshkumar, L., Rakesh, Pawan Kumar, Ramalho, Fernanda Maria Guedes, Ramalingam, Raghavendra, Ramesh, M., Ranakoti, Lalit, Sanjay, M.R., Sanliturk, Kenan Y., Santos, Caroliny, Santos, Thiago, Sarangi, Saroj Kumar, Satheeshkumar, Subramani, Sathishkumar, Tottyeapalayam Palanisamy, Sathyan, Dhanya, Savastano Junior, Holmer, Saygili, Yusuf, Shah, Atta ur Rehman, Sharma, Gagan, Siengchin, Suchart, Song, Jung-il, Sonkaria, Sanjiv, Stefanidou, M., Surip, Siti Norasmah, Surya Rajan, B., Teixeira, Ronaldo Soares, Thankachan, Titus, Venkataprasanna, K.S., Venugopal, Jayarama Reddy, Vijay, R., and Zakaria, Mohd Nazarudin

Published
2022
Full Text
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29. Multi-ancestry genome-wide smoking interaction study of 387,272 individuals identifies novel lipid loci

Author

Bentley, AR, Evangelou, E, Zhang, W, Afaq, S, Lehne, B, Poulter, N, Sever, P, Chambers, J, Elliott, P, Froguel, P, Scott, J, Cupples, A, Home Office, Medical Research Council (MRC), Action on Hearing Loss, and Imperial College Healthcare NHS Trust- BRC Funding

Subjects
11 Medical And Health Sciences, 06 Biological Sciences, Developmental Biology
Abstract

Serum lipids, such as triglycerides (TG) and high- and low-density lipoprotein cholesterol (HDL and LDL), are influenced by both genetic and lifestyle factors. Over 250 lipid loci have been identified,1-6 yet, it is unclear to what extent lifestyle factors modify the effects of these variants, or those yet to be identified. Smoking is associated with an unfavorable lipid profile,7,8 warranting its investigation as a lifestyle factor that potentially modifies genetic associations with lipids. Identifying interactions using traditional 1 degree of freedom (1df) tests of SNP x smoking terms may have low power, except in very large sample sizes. To enhance the detection of loci, a 2 degree of freedom (2df) test that jointly evaluates the interaction and main effects was developed.9 The Gene-Lifestyle Interactions Working Group, under the aegis of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium10, was formed to conduct analyses of lifestyle interactions in the genetic basis of cardiovascular traits. As both genetic and lifestyle factors differ across populations with different ancestry backgrounds, and to address the underrepresentation of non-European populations in genomic research, great effort went into creating a large, multi-ancestry resource for these investigations.11 Here, we report a genome-wide interaction study that uses both the 1df test of interaction and the 2df joint test of main and interaction effects to test the hypothesis that genetic associations of serum lipids differ by smoking status.

Published
2018

30. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Author

Feitosa, MF, Kraja, AT, Chasman, DI, Sung, YJ, Winkler, TW, Ntalla, I, Guo, X, Franceschini, N, Cheng, CY, Sim, X, Vojinovic, D, Marten, J, Musani, SK, Li, C, Bentley, AR, Brown, MR, Schwander, K, Richard, MA, Noordam, R, Aschard, H, Bartz, TM, Bielak, LF, Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, ARVR, Lohman, KK, Manning, AK, Rankinen, T, Smith, AV, Tajuddin, SM, Wojczynski, MK, Alver, M, Boissel, M, Cai, Q, Campbell, A, Chai, JF, Chen, X, Divers, J, Gao, C, Goel, A, Hagemeijer, Y, Harris, SE, He, M, Hsu, FC, Jackson, AU, Kähönen, M, Kasturiratne, A, Komulainen, P, Kühnel, B, Laguzzi, F, Luan, J, Matoba, N, Nolte, IM, Padmanabhan, S, Riaz, M, Rueedi, R, Robino, A, Said, MA, Scott, RA, Sofer, T, Stančáková, A, Takeuchi, F, Tayo, BO, Van Der Most, PJ, Varga, TV, Vitart, V, Wang, Y, Ware, EB, Warren, HR, Weiss, S, Wen, W, Yanek, LR, Zhang, W, Zhao, JH, Afaq, S, Amin, N, Amini, M, Arking, DE, Aung, T, and Boerwinkle, E

Abstract

© 2018 Public Library of Science. All Rights Reserved. Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3, 514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 × 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2, 159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Published
2018

31. Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes article

Author

Mahajan, A. Wessel, J. Willems, S.M. Zhao, W. Robertson, N.R. Chu, A.Y. Gan, W. Kitajima, H. Taliun, D. Rayner, N.W. Guo, X. Lu, Y. Li, M. Jensen, R.A. Hu, Y. Huo, S. Lohman, K.K. Zhang, W. Cook, J.P. Prins, B.P. Flannick, J. Grarup, N. Trubetskoy, V.V. Kravic, J. Kim, Y.J. Rybin, D.V. Yaghootkar, H. Müller-Nurasyid, M. Meidtner, K. Li-Gao, R. Varga, T.V. Marten, J. Li, J. Smith, A.V. An, P. Ligthart, S. Gustafsson, S. Malerba, G. Demirkan, A. Tajes, J.F. Steinthorsdottir, V. Wuttke, M. Lecoeur, C. Preuss, M. Bielak, L.F. Graff, M. Highland, H.M. Justice, A.E. Liu, D.J. Marouli, E. Peloso, G.M. Warren, H.R. Afaq, S. Afzal, S. Ahlqvist, E. Bang, L.B. Bertoni, A.G. Bombieri, C. Bork-Jensen, J. Brandslund, I. Brody, J.A. Burtt, N.P. Canouil, M. Chen, Y.-D.I. Cho, Y.S. Christensen, C. Eastwood, S.V. Eckardt, K.-U. Fischer, K. Gambaro, G. Giedraitis, V. Grove, M.L. De Haan, H.G. Hackinger, S. Hai, Y. Han, S. Tybjærg-Hansen, A. Hivert, M.-F. Isomaa, B. Jäger, S. Jørgensen, M.E. Jørgensen, T. Käräjämäki, A. Kim, B.-J. Kim, S.S. Koistinen, H.A. Kovacs, P. Kriebel, J. Kronenberg, F. Läll, K. Lange, L.A. Lee, J.-J. Lehne, B. Li, H. Lin, K.-H. Linneberg, A. Liu, C.-T. Liu, J. Loh, M. Mägi, R. Mamakou, V. McKean-Cowdin, R. Nadkarni, G. Neville, M. Nielsen, S.F. Ntalla, I. Peyser, P.A. Rathmann, W. Rice, K. Rich, S.S. Rode, L. Rolandsson, O. Schönherr, S. Selvin, E. Small, K.S. Stančáková, A. Surendran, P. Taylor, K.D. Teslovich, T.M. Thorand, B. Thorleifsson, G. Tin, A. Tönjes, A. Varbo, A. Witte, D.R. Wood, A.R. Yajnik, P. Yao, J. Yengo, L. Young, R. Boeing, H. Boerwinkle, E. Bottinger, E.P. Chowdhury, R. Dedoussis, G. Dehghan, A. Deloukas, P. Ferrario, M.M. Ferrières, J. Florez, J.C. Frossard, P. Gudnason, V. Harris, T.B. Heckbert, S.R. Howson, J.M.M. Ingelsson, M. Kathiresan, S. Kee, F. Kuusisto, J. Langenberg, C. Launer, L.J. Lindgren, C.M. Männistö, S. Meitinger, T. Mohlke, K.L. Moitry, M. Morris, A.D. Murray, A.D. De Mutsert, R. Orho-Melander, M. Owen, K.R. Perola, M. Peters, A. Province, M.A. Rasheed, A. Ridker, P.M. Rivadineira, F. Rosendaal, F.R. Rosengren, A.H. Salomaa, V. Sheu, W.H.-H. Sladek, R. Smith, B.H. Strauch, K. Uitterlinden, A.G. Varma, R. Willer, C.J. Blüher, M. Chambers, J.C. Danesh, J. Van Duijn, C. Dupuis, J. Franco, O.H. Franks, P.W. Froguel, P. Grallert, H. Groop, L. Han, B.-G. Hansen, T. Hattersley, A.T. Hayward, C. Ingelsson, E. Kardia, S.L.R. Karpe, F. Kooner, J.S. Köttgen, A. Kuulasmaa, K. Laakso, M. Lin, X. Lind, L. Liu, Y. Loos, R.J.F. Marchini, J. Metspalu, A. Mook-Kanamori, D. Nordestgaard, Bø.G. Palmer, C.N.A. Pankow, J.S. Pedersen, O. Psaty, B.M. Rauramaa, R. Sattar, N. Schulze, M.B. Soranzo, N. Spector, T.D. Stefansson, K. Stumvoll, M. Thorsteinsdottir, U. Tuomi, T. Tuomilehto, J. Wareham, N.J. Wilson, J.G. Zeggini, E. Scott, R.A. Barroso, I. Frayling, T.M. Goodarzi, M.O. Meigs, J.B. Boehnke, M. Saleheen, D. Morris, A.P. Rotter, J.I. McCarthy, M.I. ExomeBP Consortium MAGIC Consortium GIANT Consortium

Abstract

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition. © 2018 The Author(s).

Published
2018

32. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K i

Author

Feitosa, M.F. (Mary Furlan), Kraja, A. (Aldi), Chasman, D.I. (Daniel), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Marten, J. (Jonathan), Musani, S.K. (Solomon K.), Li, C. (Changwei), Bentley, A.R. (Amy), Brown, M.R., Schwander, K., Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Dorajoo, R. (Rajkumar), Fisher, V. (Virginia), Hartwig, F.P. (Fernando P.), Horimoto, A.R.V.R. (Andrea R. V.R.), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Wojczynski, M.K. (Mary ), Alver, M. (Maris), Boissel, M. (Mathilde), Cai, Q. (Qiuyin), Campbell, A. (Archie), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kähönen, M. (Mika), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Luan, J., Matoba, N. (Nana), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Riaz, M. (Muhammad), Rueedi, R. (Rico), Robino, A. (Antonietta), Said, M.A. (M. Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Vitart, V. (Veronique), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Warren, H. (Helen), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Boerwinkle, E. (Eric), Borecki, I.B. (Ingrid), Broeckel, U. (Ulrich), Brown, M. (Morris), Brumat, M. (Marco), Burke, G.L. (Greg), Canouil, M. (Mickaël), Chakravarti, A. (Aravinda), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J.M. (John M.), Correa, D.D., De Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, De Silva, H.J. (H. Janaka), Deng, X. (Xuan), Ding, J. (Jingzhong), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Ehret, G. (Georg), Eppinga, R.N. (Ruben N.), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Felix, S.B. (Stephan B.), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Gandin, I. (Ilaria), Gao, H. (He), Ghanbari, M. (Mohsen), Gigante, B. (Bruna), Gu, C. (Charles), Gu, D. (Dongfeng), Hagenaars, S. (Saskia), Hallmans, G. (Göran), Harris, T.B. (Tamara), He, J. (Jiang), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Howard, B.V. (Barbara V.), Ikram, M.K. (Kamran), John, U. (Ulrich), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas), Koh, W.-P. (Woon-Puay), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lewis, C.E. (Cora E.), Li, Y. (Yize), Lin, S. (Shiow), Liu, J. (Jianjun), Liu, J. (Jingmin), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), McKenzie, C.A. (Colin), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen), Momozawa, Y. (Yukihide), Nalls, M.A. (Michael), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), Norris, J.M. (Jill M.), O´Connell, J.R., Palmer, N.D. (Nicholette), Perls, T.T. (Thomas T.), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Roll, K. (Kathryn), Rose, L.M. (Lynda M.), Rosendaal, F.R. (Frits), Rotter, J.I. (Jerome I.), Schmidt, C.O. (Carsten Oliver), Schreiner, P.J. (Pamela), Schupf, N. (Nicole), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Sitlani, C.M. (Colleen), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Stringham, H.M. (Heather M.), Tan, N.Y.Q. (Nicholas Y.Q.), Tang, H. (Hua), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Turner, S.T. (Stephen T.), Uitterlinden, A.G. (André), Vollenweider, P. (Peter), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y.X. (Ya Xing), Wei, W.B. (Wen Bin), Williams, C. (Christine), Yao, J. (Jie), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Jonas, J.B. (Jost Bruno), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Kutalik, Z. (Zoltán), Laakso, M. (Markku), Laurie, C.C. (Cathy C.), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Oldehinkel, A.J. (Albertine), Penninx, B.W.J.H. (Brenda), Polasek, O. (Ozren), Porteous, D.J. (David J.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh J.), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Van Der Harst, P. (Pim), Wagenknecht, L.E. (Lynne), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda), Wu, T. (Tangchun), Zheng, W. (Wei), Bouchard, C. (Claude), Christensen, K. (Kaare), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Horta, B.L. (Bernardo L.), Kardia, S.L.R. (Sharon L.R.), Liu, Y. (YongMei), Pereira, A.C. (Alexandre C.), Psaty, B.M. (Bruce M.), Ridker, P.M. (Paul), Dam, R.M. (Rob) van, Gauderman, W.J. (W James), Zhu, X. (Xiaofeng), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Rotimi, C. (Charles), Cupples, L.A. (Adrienne), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (E. Shyong), Wong, T.Y. (Tien Yin), Kooperberg, C. (Charles), Palmas, W. (Walter), Rice, K.M. (Kenneth), Morrison, A.C. (Alanna), Elliott, P. (Paul), Caulfield, M. (Mark), Munroe, P. (Patricia), Rao, D.C. (Dabeeru C.), Province, M.A. (Mike), Levy, D. (Daniel), Feitosa, M.F. (Mary Furlan), Kraja, A. (Aldi), Chasman, D.I. (Daniel), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Marten, J. (Jonathan), Musani, S.K. (Solomon K.), Li, C. (Changwei), Bentley, A.R. (Amy), Brown, M.R., Schwander, K., Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Dorajoo, R. (Rajkumar), Fisher, V. (Virginia), Hartwig, F.P. (Fernando P.), Horimoto, A.R.V.R. (Andrea R. V.R.), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Wojczynski, M.K. (Mary ), Alver, M. (Maris), Boissel, M. (Mathilde), Cai, Q. (Qiuyin), Campbell, A. (Archie), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kähönen, M. (Mika), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Luan, J., Matoba, N. (Nana), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Riaz, M. (Muhammad), Rueedi, R. (Rico), Robino, A. (Antonietta), Said, M.A. (M. Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Vitart, V. (Veronique), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Warren, H. (Helen), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Boerwinkle, E. (Eric), Borecki, I.B. (Ingrid), Broeckel, U. (Ulrich), Brown, M. (Morris), Brumat, M. (Marco), Burke, G.L. (Greg), Canouil, M. (Mickaël), Chakravarti, A. (Aravinda), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J.M. (John M.), Correa, D.D., De Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, De Silva, H.J. (H. Janaka), Deng, X. (Xuan), Ding, J. (Jingzhong), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Ehret, G. (Georg), Eppinga, R.N. (Ruben N.), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Felix, S.B. (Stephan B.), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Gandin, I. (Ilaria), Gao, H. (He), Ghanbari, M. (Mohsen), Gigante, B. (Bruna), Gu, C. (Charles), Gu, D. (Dongfeng), Hagenaars, S. (Saskia), Hallmans, G. (Göran), Harris, T.B. (Tamara), He, J. (Jiang), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Howard, B.V. (Barbara V.), Ikram, M.K. (Kamran), John, U. (Ulrich), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas), Koh, W.-P. (Woon-Puay), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lewis, C.E. (Cora E.), Li, Y. (Yize), Lin, S. (Shiow), Liu, J. (Jianjun), Liu, J. (Jingmin), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), McKenzie, C.A. (Colin), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen), Momozawa, Y. (Yukihide), Nalls, M.A. (Michael), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), Norris, J.M. (Jill M.), O´Connell, J.R., Palmer, N.D. (Nicholette), Perls, T.T. (Thomas T.), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Roll, K. (Kathryn), Rose, L.M. (Lynda M.), Rosendaal, F.R. (Frits), Rotter, J.I. (Jerome I.), Schmidt, C.O. (Carsten Oliver), Schreiner, P.J. (Pamela), Schupf, N. (Nicole), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Sitlani, C.M. (Colleen), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Stringham, H.M. (Heather M.), Tan, N.Y.Q. (Nicholas Y.Q.), Tang, H. (Hua), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Turner, S.T. (Stephen T.), Uitterlinden, A.G. (André), Vollenweider, P. (Peter), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y.X. (Ya Xing), Wei, W.B. (Wen Bin), Williams, C. (Christine), Yao, J. (Jie), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Jonas, J.B. (Jost Bruno), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Kutalik, Z. (Zoltán), Laakso, M. (Markku), Laurie, C.C. (Cathy C.), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Oldehinkel, A.J. (Albertine), Penninx, B.W.J.H. (Brenda), Polasek, O. (Ozren), Porteous, D.J. (David J.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh J.), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Van Der Harst, P. (Pim), Wagenknecht, L.E. (Lynne), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda), Wu, T. (Tangchun), Zheng, W. (Wei), Bouchard, C. (Claude), Christensen, K. (Kaare), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Horta, B.L. (Bernardo L.), Kardia, S.L.R. (Sharon L.R.), Liu, Y. (YongMei), Pereira, A.C. (Alexandre C.), Psaty, B.M. (Bruce M.), Ridker, P.M. (Paul), Dam, R.M. (Rob) van, Gauderman, W.J. (W James), Zhu, X. (Xiaofeng), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Rotimi, C. (Charles), Cupples, L.A. (Adrienne), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (E. Shyong), Wong, T.Y. (Tien Yin), Kooperberg, C. (Charles), Palmas, W. (Walter), Rice, K.M. (Kenneth), Morrison, A.C. (Alanna), Elliott, P. (Paul), Caulfield, M. (Mark), Munroe, P. (Patricia), Rao, D.C. (Dabeeru C.), Province, M.A. (Mike), and Levy, D. (Daniel)

Abstract

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3, 514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 × 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2, 159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Published
2018
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33. Normal and Oblique Experimental Ballistic Impact on Bi Layered Metallic Configurations.

Author

Hussain, S., Afaq, S. K., and Kunwar, F.

Subjects
FAILURE mode & effects analysis, TUNGSTEN carbide, IMPACT (Mechanics), PROJECTILES, TUNGSTEN, METALLIC surfaces
Abstract

Experimental ballistic investigations were carried out on 03 x groups of bi layered metallic target configurations by impacting ogive shaped 7.62 x 51 mm Tungsten Carbide (WC) core Armour Piercing (AP) projectiles at normal and target oblique angles ranging from 15o to 50o. The projectiles were fired using service rifle at a distance of 10 meters in the ordnance velocity range (800±20 m/s). The three groups ballistically tested consisted of 2 x basic protection shield layout each with applique, fixed space varying angles and fixed angle varying space arrangements respectively. Aluminum 5083 with thicknesses 12.7 mm, 19.65 mm, 31.75 mm and Miilux Pro 500 Steel armour with thickness 4.32 mm were utilized for 04 x configurations whereas 02 x configurations consisted of 4.32 mm Miilux Pro 500 and 6.60 mm Rukki, Raex 500 Steel armour. Non perforation of projectile at a particular angle was taken as the performance measure. It was observed that varying the inter layer space and oblique angle with optimized configuration was able to achieve higher ballistic performance with reduced areal density. The order of the orientation of layers with same material and different thicknesses has an effect on overall ballistic performance. A substantial 43 % weight saving was observed with the optimized configuration. The failure modes, deflection of the projectile, impact and exit side diameters of the configurations were also compared. [ABSTRACT FROM AUTHOR]

Published
2021

34. STUDY ON EXTRACTS OF PARMELIA PERLATA ACH. FOR ITS ANTIMICROBIAL POTENTIAL AGAINST CERTAIN MICROORGANISMS

Author

Afaq S H, Sumbul Rehman, Abdul Latif, and Abdur Rauf

Subjects
biology, Proteus vulgaris, Bacillus cereus, Usnic acid, Pathogenic bacteria, biology.organism_classification, medicine.disease_cause, Antimicrobial, Microbiology, chemistry.chemical_compound, chemistry, Staphylococcus aureus, medicine, Antibacterial activity, Bacteria
Abstract

A significant increase in the trend of infectious diseases and alarming shoot up of resistance to existing antimicrobial agen ts demands a renew ed effort to seek agents effective against pathogenic bacteria resistant to current antimicrobials. Different extracts of Parmelia perlata (Chhadela), were studied for their screening of antibacterial activity against various bacterial strains by Agar well diffusion method on inoculated Media plates. It was found that P. perlata has a significant activity towards Bacillus cereus , Pseudomonas aeruginosa and Proteus vulgaris , Staphylococcus aureus , Corynebacterium xerosis , Escherichia coli and Klebseilla pneu omoniae while no activity towards S. epidermidis, S. mutans and S. pyrogenes . Moreover it was seen that 50 % hydro - ethanolic extracts produced more significant ZOI than 90 % ethanolic extract in all tested strains. The antibacterial activity so found, can be due to the presence of chemical constituents as Usnic acid which can halt infection and is effective against various gram - positive and gram - negative bacteria species. It can be concluded that due to their antimicrobial effects, extracts of the lichen ca n be used for the infectious diseases caused by these microbes. This study provides an in - vitro proof of the antibacterial activity of Parmelia perlata.

Published
2013

35. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author

Justice, A.E. (Anne), Winkler, T.W. (Thomas W.), Feitosa, M.F., Graff, M.J. (Maud J.L.), Fisher, V.A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J.S. (Julius S.), Ahluwalia, T.S. (Tarunveer Singh), Chu, A.Y. (Audrey Y), Heard-Costa, N.L. (Nancy), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J.D. (John D.), Kutalik, Z. (Zoltán), Xue, L. (Luting), Mahajan, A. (Anubha), Renström, F. (Frida), Wu, J.M.W. (Joseph M. W.), Qi, Q., Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L.F. (Lawrence F.), Bonnefond, A. (Amélie), Bragg-Gresham, J.L. (Jennifer L.), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M.N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Justesen, J.M. (Johanne M.), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M.E. (Marcus), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J., Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R.P.S. (Rita), Müller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A.V. (Albert), Smith, J.A. (Jennifer A), Stanča'kova, A. (Alena), Strawbridge, R.J. (Rona), Stringham, H.M. (Heather M.), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Van Der Laan, S.W. (Sander W.), Most, P.J. (Peter) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vedantam, S. (Sailaja), Verweij, N. (Niek), Vink, J.M. (Jacqueline), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zimmermann, M.E. (Martina E.), Zubair, N. (Niha), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S.J.L. (Stephan), Bartz, T.M. (Traci M.), Beilby, J.P. (John), Bergman, R.N. (Richard), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin), Braga, D. (Daniele), Buckley, B.M. (Brendan M.), Buyske, S. (Steven), Campbell, H. (Harry), Chambers, J.C. (John C.), Collins, F.S. (Francis), Curran, J.E. (Joanne), Borst, G.J. (Gert) de, Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Dedoussis, G.V. (George), Delgado, G., Ruijter, H.M. (Hester ) den, Eiriksdottir, G. (Gudny), Eriksson, A.L. (Anna L.), Esko, T. (Tõnu), Faul, J.D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T.B. (Tanja), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Göran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T.B. (Tamara), Hartman, C.A. (C.), Hassinen, M. (Maija), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hindorff, L.A. (Lucia A), Hocking, L.J., Hollensted, M. (Mette), Holmen, O.L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. (Alan), Jansson, J.-O. (John-Olov), Jarvelin, M.-R. (Marjo-Riitta), Jhun, M.A. (Min A.), Jørgensen, M.E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Krämer, B.K. (Bernhard), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Leander, K. (Karin), Lee, N.R. (Nanette R.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stéphane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G.H. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P.A. (Pamela), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N.G. (Nicholas), McKenzie, C.A. (Colin), McKnight, B. (Barbara), Mellström, D. (Dan), Menni, C. (Cristina), Montgomery, G.W. (Grant W.), Musk, A.W. (Arthur), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I.M. (Ilja), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Ong, K.K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P.A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D.J. (David J.), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rao, D.C. (D. C.), Rasmussen-Torvik, L.J. (Laura), Rawal, R. (Rajesh), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Rose, L.M. (Lynda M.), Bien, S.A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M.A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R.A. (Robert), Sennblad, B. (Bengt), Siemelink, M.A. (Marten A.), Silbernagel, G. (Günther), Slagboom, P.E. (Eline), Snieder, H. (Harold), Staessen, J.A. (Jan A.), Stott, D.J. (David. J.), Swertz, M.A. (Morris A.), Swift, A.J. (Amy), Taylor, K.D. (Kent), Tayo, B. (Bamidele), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Völzke, H. (Henry), Vonk, J.M. (Judith), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Westendorp, R.G.J. (Rudi), Wild, S.H. (Sarah), Willemsen, G., Wolffenbuttel, B.H.R. (Bruce), Wong, A. (Andrew), Wright, A.F. (Alan), Zhao, W. (Wei), Zillikens, M.C. (Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Böger, C.A. (Carsten), Boomsma, D.I. (Dorret), Bouchard, C. (Claude), Bruinenberg, M. (M.), Chasman, D.I. (Daniel), Ida Chen, Y.-D. (Yii-Der), Chines, P.S. (Peter), Cooper, R.S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), Faire, U. (Ulf) de, Ferrucci, L. (Luigi), Franks, P.W. (Paul), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.J. (Hans Jörgen), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A.D. (Andrew D.), Jukema, J.W. (Jan Wouter), Kardia, S.L.R. (Sharon), Kivimaki, M. (Mika), Kooner, J.S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), März, W. (Winfried), McCarthy, M.I. (Mark), Metspalu, A. (Andres), Morris, A.P. (Andrew), Ohlsson, C. (Claes), Palmer, L.J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B.H. (Blair), Sørensen, T.I.A. (Thorkild), Strauch, K. (Konstantin), Tiemeier, H.W. (Henning), Tremoli, E. (Elena), Van Der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N.J. (Nick), Weir, D.R. (David), Whitfield, J. (John), Wilson, J.F. (James F.), Tyrrell, A.W.R., Frayling, T.M. (Timothy M.), Barroso, I.E. (Inês), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Hirschhorn, J.N. (Joel), Hunter, D.J. (David J.), Spector, T.D. (Timothy), Strachan, D.P. (David), Duijn, C.M. (Cornelia) van, Heid, I.M. (Iris), Mohlke, K.L. (Karen), Marchini, J. (Jonathan), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Liu, C.-T. (Ching-Ti), Borecki, I.B. (Ingrid), North, K.E. (Kari), Cupples, L.A. (Adrienne), Justice, A.E. (Anne), Winkler, T.W. (Thomas W.), Feitosa, M.F., Graff, M.J. (Maud J.L.), Fisher, V.A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J.S. (Julius S.), Ahluwalia, T.S. (Tarunveer Singh), Chu, A.Y. (Audrey Y), Heard-Costa, N.L. (Nancy), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J.D. (John D.), Kutalik, Z. (Zoltán), Xue, L. (Luting), Mahajan, A. (Anubha), Renström, F. (Frida), Wu, J.M.W. (Joseph M. W.), Qi, Q., Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L.F. (Lawrence F.), Bonnefond, A. (Amélie), Bragg-Gresham, J.L. (Jennifer L.), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M.N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Justesen, J.M. (Johanne M.), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M.E. (Marcus), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J., Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R.P.S. (Rita), Müller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A.V. (Albert), Smith, J.A. (Jennifer A), Stanča'kova, A. (Alena), Strawbridge, R.J. (Rona), Stringham, H.M. (Heather M.), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Van Der Laan, S.W. (Sander W.), Most, P.J. (Peter) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vedantam, S. (Sailaja), Verweij, N. (Niek), Vink, J.M. (Jacqueline), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zimmermann, M.E. (Martina E.), Zubair, N. (Niha), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S.J.L. (Stephan), Bartz, T.M. (Traci M.), Beilby, J.P. (John), Bergman, R.N. (Richard), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin), Braga, D. (Daniele), Buckley, B.M. (Brendan M.), Buyske, S. (Steven), Campbell, H. (Harry), Chambers, J.C. (John C.), Collins, F.S. (Francis), Curran, J.E. (Joanne), Borst, G.J. (Gert) de, Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Dedoussis, G.V. (George), Delgado, G., Ruijter, H.M. (Hester ) den, Eiriksdottir, G. (Gudny), Eriksson, A.L. (Anna L.), Esko, T. (Tõnu), Faul, J.D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T.B. (Tanja), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Göran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T.B. (Tamara), Hartman, C.A. (C.), Hassinen, M. (Maija), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hindorff, L.A. (Lucia A), Hocking, L.J., Hollensted, M. (Mette), Holmen, O.L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. (Alan), Jansson, J.-O. (John-Olov), Jarvelin, M.-R. (Marjo-Riitta), Jhun, M.A. (Min A.), Jørgensen, M.E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Krämer, B.K. (Bernhard), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Leander, K. (Karin), Lee, N.R. (Nanette R.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stéphane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G.H. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P.A. (Pamela), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N.G. (Nicholas), McKenzie, C.A. (Colin), McKnight, B. (Barbara), Mellström, D. (Dan), Menni, C. (Cristina), Montgomery, G.W. (Grant W.), Musk, A.W. (Arthur), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I.M. (Ilja), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Ong, K.K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P.A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D.J. (David J.), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rao, D.C. (D. C.), Rasmussen-Torvik, L.J. (Laura), Rawal, R. (Rajesh), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Rose, L.M. (Lynda M.), Bien, S.A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M.A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R.A. (Robert), Sennblad, B. (Bengt), Siemelink, M.A. (Marten A.), Silbernagel, G. (Günther), Slagboom, P.E. (Eline), Snieder, H. (Harold), Staessen, J.A. (Jan A.), Stott, D.J. (David. J.), Swertz, M.A. (Morris A.), Swift, A.J. (Amy), Taylor, K.D. (Kent), Tayo, B. (Bamidele), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Völzke, H. (Henry), Vonk, J.M. (Judith), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Westendorp, R.G.J. (Rudi), Wild, S.H. (Sarah), Willemsen, G., Wolffenbuttel, B.H.R. (Bruce), Wong, A. (Andrew), Wright, A.F. (Alan), Zhao, W. (Wei), Zillikens, M.C. (Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Böger, C.A. (Carsten), Boomsma, D.I. (Dorret), Bouchard, C. (Claude), Bruinenberg, M. (M.), Chasman, D.I. (Daniel), Ida Chen, Y.-D. (Yii-Der), Chines, P.S. (Peter), Cooper, R.S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), Faire, U. (Ulf) de, Ferrucci, L. (Luigi), Franks, P.W. (Paul), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.J. (Hans Jörgen), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A.D. (Andrew D.), Jukema, J.W. (Jan Wouter), Kardia, S.L.R. (Sharon), Kivimaki, M. (Mika), Kooner, J.S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), März, W. (Winfried), McCarthy, M.I. (Mark), Metspalu, A. (Andres), Morris, A.P. (Andrew), Ohlsson, C. (Claes), Palmer, L.J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B.H. (Blair), Sørensen, T.I.A. (Thorkild), Strauch, K. (Konstantin), Tiemeier, H.W. (Henning), Tremoli, E. (Elena), Van Der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N.J. (Nick), Weir, D.R. (David), Whitfield, J. (John), Wilson, J.F. (James F.), Tyrrell, A.W.R., Frayling, T.M. (Timothy M.), Barroso, I.E. (Inês), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Hirschhorn, J.N. (Joel), Hunter, D.J. (David J.), Spector, T.D. (Timothy), Strachan, D.P. (David), Duijn, C.M. (Cornelia) van, Heid, I.M. (Iris), Mohlke, K.L. (Karen), Marchini, J. (Jonathan), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Liu, C.-T. (Ching-Ti), Borecki, I.B. (Ingrid), North, K.E. (Kari), and Cupples, L.A. (Adrienne)

Abstract

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting

Published
2017
Full Text
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36. CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Author

Mace, A. (Aurelien), Tuke, M.A. (Marcus A.), Deelen, P. (Patrick), Kristiansson, K. (Kati), Mattsson, H. (Hannele), Nõukas, M. (Margit), Sapkota, Y. (Yadav), Schick, U.M. (Ursula), Porcu, E. (Eleonora), Rüeger, S. (Sina), McDaid, A.F. (Aaron F.), Porteous, D.J. (David J.), Winkler, T.W. (Thomas W.), Salvi, E. (Erika), Shrine, N.R.G. (Nick), Liu, X. (Xueping), Ang, W.Q. (Wei), Zhang, W. (Weihua), Feitosa, M.F., Venturini, C. (Cristina), Most, P.J. (Peter) van der, Rosengren, A. (Anders), Wood, A.R. (Andrew), Beaumont, R.N. (Robin N.), Jones, S.E. (Samuel E.), Ruth, K.S. (Katherine S.), Yaghootkar, H. (Hanieh), Tyrrell, A.W.R., Havulinna, A.S. (Aki), Boers, H. (Harmen), Mägi, R. (Reedik), Kriebel, J. (Jennifer), Müller-Nurasyid, M. (Martina), Perola, M. (Markus), Nieminen, M.S. (Markku), Lokki, M.L., Kähönen, M. (Mika), Viikari, J. (Jorma), Geller, F. (Frank), Lahti, J., Palotie, A. (Aarno), Koponen, P. (Päivikki), Lundqvist, A. (Annamari), Rissanen, H. (Harri), Bottinger, E.P. (Erwin), Afaq, S. (Saima), Wojczynski, M.K. (Mary ), Lenzini, P. (Petra), Nolte, I.M. (Ilja), Sparsø, T. (Thomas), Schupf, N. (Nicole), Christensen, K. (Kaare), Perls, T.T. (Thomas T.), Newman, A.B. (Anne B.), Werge, T.M. (Thomas), Snieder, H. (Harold), Spector, T.D. (Timothy), Chambers, J.C. (John C.), Koskinen, S. (Seppo), Melbye, M. (Mads), Raitakari, O.T. (Olli T.), Lehtimäki, T. (Terho), Tobin, M.D. (Martin), Wain, L.V. (Louise V.), Sinisalo, J. (Juha), Peters, A. (Annette), Meitinger, T. (Thomas), Martin, N.G. (Nicholas), Wray, N.R. (Naomi), Montgomery, G.W. (Grant W.), Medland, S.E. (Sarah), Swertz, M.A. (Morris A.), Vartiainen, E. (Erkki), Borodulin, K. (Katja), Männistö, S. (Satu), Murray, A. (Anna), Bochud, M. (Murielle), Jacquemont, S. (Sébastien), Rivadeneira, F. (Fernando), Hansen, T. (Thomas), Oldehinkel, A.J. (Albertine), Mangino, M. (Massimo), Province, M.A. (Mike), Deloukas, P. (Panos), Kooner, J.S. (Jaspal S.), Freathy, R.M. (Rachel), Pennell, C.E. (Craig), Feenstra, B. (Bjarke), Strachan, D.P. (David), Lettre, G. (Guillaume), Hirschhorn, J.N. (Joel), Cusi, D. (Daniele), Heid, I.M. (Iris), Hayward, C. (Caroline), Männik, K. (Katrin), Beckmann, J.S. (Jacques), Loos, R.J.F. (Ruth), Nyholt, D.R. (Dale), Metspalu, A. (Andres), Hagen, K. (Knut), Weedon, M.N. (Michael), Salomaa, V. (Veikko), Franke, L. (Lude), Reymond, A. (Alexandre), Frayling, T.M. (Timothy M.), Kutalik, Z. (Zoltán), Mace, A. (Aurelien), Tuke, M.A. (Marcus A.), Deelen, P. (Patrick), Kristiansson, K. (Kati), Mattsson, H. (Hannele), Nõukas, M. (Margit), Sapkota, Y. (Yadav), Schick, U.M. (Ursula), Porcu, E. (Eleonora), Rüeger, S. (Sina), McDaid, A.F. (Aaron F.), Porteous, D.J. (David J.), Winkler, T.W. (Thomas W.), Salvi, E. (Erika), Shrine, N.R.G. (Nick), Liu, X. (Xueping), Ang, W.Q. (Wei), Zhang, W. (Weihua), Feitosa, M.F., Venturini, C. (Cristina), Most, P.J. (Peter) van der, Rosengren, A. (Anders), Wood, A.R. (Andrew), Beaumont, R.N. (Robin N.), Jones, S.E. (Samuel E.), Ruth, K.S. (Katherine S.), Yaghootkar, H. (Hanieh), Tyrrell, A.W.R., Havulinna, A.S. (Aki), Boers, H. (Harmen), Mägi, R. (Reedik), Kriebel, J. (Jennifer), Müller-Nurasyid, M. (Martina), Perola, M. (Markus), Nieminen, M.S. (Markku), Lokki, M.L., Kähönen, M. (Mika), Viikari, J. (Jorma), Geller, F. (Frank), Lahti, J., Palotie, A. (Aarno), Koponen, P. (Päivikki), Lundqvist, A. (Annamari), Rissanen, H. (Harri), Bottinger, E.P. (Erwin), Afaq, S. (Saima), Wojczynski, M.K. (Mary ), Lenzini, P. (Petra), Nolte, I.M. (Ilja), Sparsø, T. (Thomas), Schupf, N. (Nicole), Christensen, K. (Kaare), Perls, T.T. (Thomas T.), Newman, A.B. (Anne B.), Werge, T.M. (Thomas), Snieder, H. (Harold), Spector, T.D. (Timothy), Chambers, J.C. (John C.), Koskinen, S. (Seppo), Melbye, M. (Mads), Raitakari, O.T. (Olli T.), Lehtimäki, T. (Terho), Tobin, M.D. (Martin), Wain, L.V. (Louise V.), Sinisalo, J. (Juha), Peters, A. (Annette), Meitinger, T. (Thomas), Martin, N.G. (Nicholas), Wray, N.R. (Naomi), Montgomery, G.W. (Grant W.), Medland, S.E. (Sarah), Swertz, M.A. (Morris A.), Vartiainen, E. (Erkki), Borodulin, K. (Katja), Männistö, S. (Satu), Murray, A. (Anna), Bochud, M. (Murielle), Jacquemont, S. (Sébastien), Rivadeneira, F. (Fernando), Hansen, T. (Thomas), Oldehinkel, A.J. (Albertine), Mangino, M. (Massimo), Province, M.A. (Mike), Deloukas, P. (Panos), Kooner, J.S. (Jaspal S.), Freathy, R.M. (Rachel), Pennell, C.E. (Craig), Feenstra, B. (Bjarke), Strachan, D.P. (David), Lettre, G. (Guillaume), Hirschhorn, J.N. (Joel), Cusi, D. (Daniele), Heid, I.M. (Iris), Hayward, C. (Caroline), Männik, K. (Katrin), Beckmann, J.S. (Jacques), Loos, R.J.F. (Ruth), Nyholt, D.R. (Dale), Metspalu, A. (Andres), Hagen, K. (Knut), Weedon, M.N. (Michael), Salomaa, V. (Veikko), Franke, L. (Lude), Reymond, A. (Alexandre), Frayling, T.M. (Timothy M.), and Kutalik, Z. (Zoltán)

Abstract

There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m2). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increa

Published
2017
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37. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author

Justice, A. E. (Anne E.), Winkler, T. W. (Thomas W.), Feitosa, M. F. (Mary F.), Graff, M. (Misa), Fisher, V. A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J. S. (Julius S.), Ahluwalia, T. S. (Tarunveer S.), Chu, A. Y. (Audrey Y.), Heard-Costa, N. L. (Nancy L.), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J. D. (John D.), Kutalik, Z. (Zoltan), Xue, L. (Luting), Mahajan, A. (Anubha), Renstrom, F. (Frida), Wu, J. (Joseph), Qi, Q. (Qibin), Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L. F. (Lawrence F.), Bonnefond, A. (Amelie), Bragg, J. (Jennifer), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M. N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J. E. (Jennifer E.), Jackson, A. U. (Anne U.), Justesen, J. M. (Johanne Marie), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M. E. (Marcus E.), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R. P. (Rita P. S.), Mueller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A. V. (Albert Vernon), Smith, J. A. (Jennifer A.), Stancakova, A. (Alena), Strawbridge, R. J. (Rona J.), Stringham, H. M. (Heather M.), Sung, Y. J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), van der Laan, S. W. (Sander W.), van der Most, P. J. (Peter J.), Van Vliet-Ostaptchouk, J. V. (Jana V.), Vedantam, S. L. (Sailaja L.), Verweij, N. (Niek), Vink, J. M. (Jacqueline M.), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zimmermann, M. E. (Martina E.), Zubair, N. (Niha), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S. J. (Stephan J. L.), Bartz, T. M. (Traci M.), Beilby, J. (John), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Bottinger, E. (Erwin), Braga, D. (Daniele), Buckley, B. M. (Brendan M.), Buyske, S. (Steve), Campbell, H. (Harry), Chambers, J. C. (John C.), Collins, F. S. (Francis S.), Curran, J. E. (Joanne E.), de Borst, G. J. (Gert J.), de Craen, A. J. (Anton J. M.), de Geus, E. J. (Eco J. C.), Dedoussis, G. (George), Delgado, G. E. (Graciela E.), den Ruijter, H. M. (Hester M.), Eiriksdottir, G. (Gudny), Eriksson, A. L. (Anna L.), Esko, T. (Tonu), Faul, J. D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T. B. (Tanja B.), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Goran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T. B. (Tamara B.), Hartman, C. A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. D. (Nicholas D.), Heath, A. C. (Andrew C.), Hernandez, D. (Dena), Hindorff, L. (Lucia), Hocking, L. J. (Lynne J.), Hollensted, M. (Mette), Holmen, O. L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J. J. (Jouke Jan), Huang, J. (Jie), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. L. (Alan L.), Jansson, J.-O. (John-Olov), Järvelin, M.-R. (Marjo-Riitta), Jhun, M. A. (Min A.), Jorgensen, M. E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Kramer, B. K. (Bernhard K.), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Leander, K. (Karin), Lee, N. R. (Nanette R.), Lind, L. (Lars), Lindgren, C. M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stephane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P. A. (Pamela A. F.), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N. G. (Nicholas G.), McKenzie, C. A. (Colin A.), McKnight, B. (Barbara), Mellstrom, D. (Dan), Menni, C. (Cristina), Montgomery, G. W. (Grant W.), Musk, A. W. (A. W. (Bill)), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I. M. (Ilja M.), Oldehinkel, A. J. (Albertine J.), Olden, M. (Matthias), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P. A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D. J. (David J.), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rao, D. C. (D. C.), Rasmussen-Torvik, L. J. (Laura J.), Rawal, R. (Rajesh), Rice, T. (Treva), Ridker, P. M. (Paul M.), Rose, L. M. (Lynda M.), Bien, S. A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M. A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R. A. (Robert A.), Sennblad, B. (Bengt), Siemelink, M. A. (Marten A.), Silbernagel, G. (Gunther), Slagboom, P. E. (P. Eline), Snieder, H. (Harold), Staessen, J. A. (Jan A.), Stott, D. J. (David J.), Swertz, M. A. (Morris A.), Swift, A. J. (Amy J.), Taylor, K. D. (Kent D.), Tayo, B. O. (Bamidele O.), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A. G. (Andre G.), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Volzke, H. (Henry), Vonk, J. M. (Judith M.), Waeber, G. (Gerard), Waldenberger, M. (Melanie), Westendorp, R. G. (R. G. J.), Wild, S. (Sarah), Willemsen, G. (Gonneke), Wolffenbuttel, B. H. (Bruce H. R.), Wong, A. (Andrew), Wright, A. F. (Alan F.), Zhao, W. (Wei), Zillikens, M. C. (M. Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Boger, C. A. (Carsten A.), Boomsma, D. I. (Dorret I.), Bouchard, C. (Claude), Bruinenberg, M. (Marcel), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Chines, P. S. (Peter S.), Cooper, R. S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), de Faire, U. (Ulf), Ferrucci, L. (Luigi), Franks, P. W. (Paul W.), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.-J. (Hans-Jorgen), Gudnason, V. (Vilmundur), Haiman, C. A. (Christopher A.), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A. D. (Andrew D.), Jukema, W. (Wouter), Kardia, S. L. (Sharon L. R.), Kivimäki, M. (Mika), Kooner, J. S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), Marz, W. (Winfried), McCarthy, M. I. (Mark I.), Metspalu, A. (Andres), Morris, A. P. (Andrew P.), Ohlsson, C. (Claes), Palmer, L. J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B. H. (Blair H.), Sorensen, T. I. (Thorkild I. A.), Strauch, K. (Konstantin), Tiemeier, H. (Henning), Tremoli, E. (Elena), Van der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N. J. (Nicholas J.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wilson, J. F. (James F.), Tyrrell, J. (Jessica), Frayling, T. M. (Timothy M.), Barroso, I. (Ines), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C. S. (Caroline S.), Hirschhorn, J. N. (Joel N.), Hunter, D. J. (David J.), Spector, T. D. (Tim D.), Strachan, D. P. (David P.), van Duijn, C. M. (Cornelia M.), Heid, I. M. (Iris M.), Mohlke, K. L. (Karen L.), Marchini, J. (Jonathan), Loos, R. J. (Ruth J. F.), Kilpeläinen, T. O. (Tuomas O.), Liu, C.-T. (Ching-Ti), Borecki, I. B. (Ingrid B.), North, K. E. (Kari E.), Cupples, L. A. (L. Adrienne), Justice, A. E. (Anne E.), Winkler, T. W. (Thomas W.), Feitosa, M. F. (Mary F.), Graff, M. (Misa), Fisher, V. A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J. S. (Julius S.), Ahluwalia, T. S. (Tarunveer S.), Chu, A. Y. (Audrey Y.), Heard-Costa, N. L. (Nancy L.), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J. D. (John D.), Kutalik, Z. (Zoltan), Xue, L. (Luting), Mahajan, A. (Anubha), Renstrom, F. (Frida), Wu, J. (Joseph), Qi, Q. (Qibin), Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L. F. (Lawrence F.), Bonnefond, A. (Amelie), Bragg, J. (Jennifer), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M. N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J. E. (Jennifer E.), Jackson, A. U. (Anne U.), Justesen, J. M. (Johanne Marie), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M. E. (Marcus E.), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R. P. (Rita P. S.), Mueller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A. V. (Albert Vernon), Smith, J. A. (Jennifer A.), Stancakova, A. (Alena), Strawbridge, R. J. (Rona J.), Stringham, H. M. (Heather M.), Sung, Y. J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), van der Laan, S. W. (Sander W.), van der Most, P. J. (Peter J.), Van Vliet-Ostaptchouk, J. V. (Jana V.), Vedantam, S. L. (Sailaja L.), Verweij, N. (Niek), Vink, J. M. (Jacqueline M.), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zimmermann, M. E. (Martina E.), Zubair, N. (Niha), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S. J. (Stephan J. L.), Bartz, T. M. (Traci M.), Beilby, J. (John), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Bottinger, E. (Erwin), Braga, D. (Daniele), Buckley, B. M. (Brendan M.), Buyske, S. (Steve), Campbell, H. (Harry), Chambers, J. C. (John C.), Collins, F. S. (Francis S.), Curran, J. E. (Joanne E.), de Borst, G. J. (Gert J.), de Craen, A. J. (Anton J. M.), de Geus, E. J. (Eco J. C.), Dedoussis, G. (George), Delgado, G. E. (Graciela E.), den Ruijter, H. M. (Hester M.), Eiriksdottir, G. (Gudny), Eriksson, A. L. (Anna L.), Esko, T. (Tonu), Faul, J. D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T. B. (Tanja B.), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Goran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T. B. (Tamara B.), Hartman, C. A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. D. (Nicholas D.), Heath, A. C. (Andrew C.), Hernandez, D. (Dena), Hindorff, L. (Lucia), Hocking, L. J. (Lynne J.), Hollensted, M. (Mette), Holmen, O. L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J. J. (Jouke Jan), Huang, J. (Jie), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. L. (Alan L.), Jansson, J.-O. (John-Olov), Järvelin, M.-R. (Marjo-Riitta), Jhun, M. A. (Min A.), Jorgensen, M. E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Kramer, B. K. (Bernhard K.), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Leander, K. (Karin), Lee, N. R. (Nanette R.), Lind, L. (Lars), Lindgren, C. M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stephane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P. A. (Pamela A. F.), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N. G. (Nicholas G.), McKenzie, C. A. (Colin A.), McKnight, B. (Barbara), Mellstrom, D. (Dan), Menni, C. (Cristina), Montgomery, G. W. (Grant W.), Musk, A. W. (A. W. (Bill)), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I. M. (Ilja M.), Oldehinkel, A. J. (Albertine J.), Olden, M. (Matthias), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P. A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D. J. (David J.), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rao, D. C. (D. C.), Rasmussen-Torvik, L. J. (Laura J.), Rawal, R. (Rajesh), Rice, T. (Treva), Ridker, P. M. (Paul M.), Rose, L. M. (Lynda M.), Bien, S. A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M. A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R. A. (Robert A.), Sennblad, B. (Bengt), Siemelink, M. A. (Marten A.), Silbernagel, G. (Gunther), Slagboom, P. E. (P. Eline), Snieder, H. (Harold), Staessen, J. A. (Jan A.), Stott, D. J. (David J.), Swertz, M. A. (Morris A.), Swift, A. J. (Amy J.), Taylor, K. D. (Kent D.), Tayo, B. O. (Bamidele O.), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A. G. (Andre G.), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Volzke, H. (Henry), Vonk, J. M. (Judith M.), Waeber, G. (Gerard), Waldenberger, M. (Melanie), Westendorp, R. G. (R. G. J.), Wild, S. (Sarah), Willemsen, G. (Gonneke), Wolffenbuttel, B. H. (Bruce H. R.), Wong, A. (Andrew), Wright, A. F. (Alan F.), Zhao, W. (Wei), Zillikens, M. C. (M. Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Boger, C. A. (Carsten A.), Boomsma, D. I. (Dorret I.), Bouchard, C. (Claude), Bruinenberg, M. (Marcel), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Chines, P. S. (Peter S.), Cooper, R. S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), de Faire, U. (Ulf), Ferrucci, L. (Luigi), Franks, P. W. (Paul W.), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.-J. (Hans-Jorgen), Gudnason, V. (Vilmundur), Haiman, C. A. (Christopher A.), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A. D. (Andrew D.), Jukema, W. (Wouter), Kardia, S. L. (Sharon L. R.), Kivimäki, M. (Mika), Kooner, J. S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), Marz, W. (Winfried), McCarthy, M. I. (Mark I.), Metspalu, A. (Andres), Morris, A. P. (Andrew P.), Ohlsson, C. (Claes), Palmer, L. J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B. H. (Blair H.), Sorensen, T. I. (Thorkild I. A.), Strauch, K. (Konstantin), Tiemeier, H. (Henning), Tremoli, E. (Elena), Van der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N. J. (Nicholas J.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wilson, J. F. (James F.), Tyrrell, J. (Jessica), Frayling, T. M. (Timothy M.), Barroso, I. (Ines), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C. S. (Caroline S.), Hirschhorn, J. N. (Joel N.), Hunter, D. J. (David J.), Spector, T. D. (Tim D.), Strachan, D. P. (David P.), van Duijn, C. M. (Cornelia M.), Heid, I. M. (Iris M.), Mohlke, K. L. (Karen L.), Marchini, J. (Jonathan), Loos, R. J. (Ruth J. F.), Kilpeläinen, T. O. (Tuomas O.), Liu, C.-T. (Ching-Ti), Borecki, I. B. (Ingrid B.), North, K. E. (Kari E.), and Cupples, L. A. (L. Adrienne)

Abstract

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

Published
2017

38. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author

Justice, AE, Winkler, TW, Feitosa, MF, Graff, M, Fisher, V A, Young, K, Barata, L, Deng, X, Czajkowski, J, Hadley, D, Ngwa, JS, Ahluwalia, TS, Chu, AY, Heard-Costa, NL, Lim, E, Perez, J, Eicher, JD, Kutalik, Z, Xue, L, Mahajan, A, Renstrom, F, Wu, J, Qi, QB, Ahmad, Shahzad, Alfred, T, Amin, Najaf, Bielak, LF, Bonnefond, A, Bragg, J, Cadby, G, Chittani, M, Coggeshall, S, Corre, T, Direk, N, Eriksson, J, Fischer, K, Gorski, M, Harder, MN, Horikoshi, M, Huang, T, Huffman, JE, Jackson, AU, Justesen, JM, Kanoni, S, Kinnunen, L, Kleber, ME, Komulainen, P, Kumari, M, Lim, U, Luan, J, Lyytikainen, LP, Mangino, M, Manichaikul, A, Marten, J, Middelberg, RPS, Mueller-Nurasyid, M, Navarro, P, Perusse, L, Pervjakova, N, Sarti, C, Smith, AV, Smith, JA, Stancakova, A, Strawbridge, RJ, Stringham, HM, Sung, YJ, Tanaka, T, Teumer, A, Trompet, S, van der Laan, SW, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vedantam, SL, Verweij, N (Niek), Vink, JM, Vitart, V, Wu, Fenny, Yengo, L, Zhang, WH, Zhao, JH, Zimmermann, ME, Zubair, N, Abecasis, GR, Adair, LS, Afaq, S, Afzal, U, Bakker, SJL, Bartz, TM, Beilby, J, Bergman, RN, Bergmann, S, Biffar, R, Blangero, J, Boerwinkle, E, Bonnycastle, LL, Bottinger, E, Braga, D, Buckley, BM, Buyske, S, Campbell, H, Chambers, JC, Collins, FS, Curran, JE, de Borst, GJ, de Craen, AJM, de Geus, EJC, Dedoussis, G, Delgado, GE, den Ruijter, HM, Eiriksdottir, G, Eriksson, AL, Esko, T, Faul, JD, Ford, I, Forrester, T, Gertow, K, Gigante, B, Glorioso, N, Gong, J, Grallert, H, Grammer, TB, Grarup, N, Haitjema, S, Hallmans, G, Hamsten, A, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, ND, Heath, AC, Hernandez, D, Hindorff, L, Hocking, LJ, Hollensted, M, Holmen, OL, Homuth, G, Hottenga, JJ, Huang, J, Hung, J, Hutri-Kahonen, N, Ingelsson, E, James, AL, Jansson, JO, Jarvelin, MR, Jhun, MA, Jorgensen, ME, Juonala, M, Kahonen, M, Karlsson, M, Koistinen, HA, Kolcic, I, Kolovou, G, Kooperberg, C, Kramer, BK, Kuusisto, J, Kvaloy, K, Lakka, TA, Langenberg, C, Launer, LJ, Leander, K, Lee, NR, Lind, L, Lindgren, CM, Linneberg, A, Lobbens, S, Loh, M, Lorentzon, M, Luben, R, Lubke, G, Ludolph-Donislawski, A, Lupoli, S, Madden, PAF, Mannikko, R, Marques-Vidal, P, Martin, NG, McKenzie, CA, McKnight, B, Mellstrom, D, Menni, C, Montgomery, GW, Musk, AW, Narisu, N, Nauck, M, Nolte, IM, Oldehinkel, AJ, Olden, M, Ong, KK, Padmanabhan, S, Peyser, PA, Pisinger, C, Porteous, DJ, Raitakari, OT, Rankinen, T, Rao, DC, Rasmussen-Torvik, LJ, Rawal, R, Rice, T, Ridker, PM, Rose, LM, Bien, SA, Rudan, I, Sanna, S, Sarzynski, MA, Sattar, N, Savonen, K, Schlessinger, D, Scholtens, s, Schurmann, C, Scott, RA, Sennblad, B, Siemelink, MA, Silbernagel, G, Slagboom, PE (Eline), Snieder, H, Staessen, JA, Stott, DJ, Swertz, MA, Swift, AJ, Taylor, KD, Tayo, BO, Thorand, B, Thuillier, D, Tuomilehto, J, Uitterlinden, André, Vandenput, L, Vohl, MC, Volzke, H, Vonk, JM, Waeber, G, Waldenberger, M, Westendorp, RGJ, Wild, S, Willemsen, G, Wolffenbuttel, BHR, Wong, A, Wright, AF, Zhao, W, Zillikens, M.C., Baldassarre, D, Balkau, B, Bandinelli, S, Boger, CA, Boomsma, DI, Bouchard, C, Bruinenberg, M, Chasman, DI, Chen, YDI, Chines, PS, Cooper, RS, Cucca, F, Cusi, D, de Faire, U, Ferrucci, L, Franks, PW, Froguel, P, Gordon-Larsen, P, Grabe, HJ, Gudnason, V, Haiman, CA, Hayward, C, Hveem, K, Johnson, AD, Jukema, W, Kardia, SLR, Kivimaki, M, Kooner, JS, Kuh, D, Laakso, M, Lehtimaki, T, Le Marchand, L, Marz, W, McCarthy, MI, Metspalu, A, Morris, AP, Ohlsson, C, Palmer, LJ, Pasterkamp, G, Pedersen, O, Peters, A, Peters, U, Polasek, O, Psaty, BM, Qi, L, Rauramaa, R, Smith, BH, Sorensen, TIA, Strauch, K, Tiemeier, Henning, Tremoli, E, van der Harst, P, Vestergaard, H, Vollenweider, P, Wareham, NJ, Weir, DR, Whitfield, JB, Wilson, JF, Tyrrell, J, Frayling, TM, Barroso, I, Boehnke, M, Deloukas, P, Fox, CS, Hirschhorn, JN, Hunter, DJ, Spector, TD, Strachan, DP, Duijn, Cornelia, Heid, IM, Mohlke, KL, Marchini, J, Loos, RJF, Kilpelainen, TO, Liu, CT, Borecki, IB, North, KE, Cupples, LA, Justice, AE, Winkler, TW, Feitosa, MF, Graff, M, Fisher, V A, Young, K, Barata, L, Deng, X, Czajkowski, J, Hadley, D, Ngwa, JS, Ahluwalia, TS, Chu, AY, Heard-Costa, NL, Lim, E, Perez, J, Eicher, JD, Kutalik, Z, Xue, L, Mahajan, A, Renstrom, F, Wu, J, Qi, QB, Ahmad, Shahzad, Alfred, T, Amin, Najaf, Bielak, LF, Bonnefond, A, Bragg, J, Cadby, G, Chittani, M, Coggeshall, S, Corre, T, Direk, N, Eriksson, J, Fischer, K, Gorski, M, Harder, MN, Horikoshi, M, Huang, T, Huffman, JE, Jackson, AU, Justesen, JM, Kanoni, S, Kinnunen, L, Kleber, ME, Komulainen, P, Kumari, M, Lim, U, Luan, J, Lyytikainen, LP, Mangino, M, Manichaikul, A, Marten, J, Middelberg, RPS, Mueller-Nurasyid, M, Navarro, P, Perusse, L, Pervjakova, N, Sarti, C, Smith, AV, Smith, JA, Stancakova, A, Strawbridge, RJ, Stringham, HM, Sung, YJ, Tanaka, T, Teumer, A, Trompet, S, van der Laan, SW, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vedantam, SL, Verweij, N (Niek), Vink, JM, Vitart, V, Wu, Fenny, Yengo, L, Zhang, WH, Zhao, JH, Zimmermann, ME, Zubair, N, Abecasis, GR, Adair, LS, Afaq, S, Afzal, U, Bakker, SJL, Bartz, TM, Beilby, J, Bergman, RN, Bergmann, S, Biffar, R, Blangero, J, Boerwinkle, E, Bonnycastle, LL, Bottinger, E, Braga, D, Buckley, BM, Buyske, S, Campbell, H, Chambers, JC, Collins, FS, Curran, JE, de Borst, GJ, de Craen, AJM, de Geus, EJC, Dedoussis, G, Delgado, GE, den Ruijter, HM, Eiriksdottir, G, Eriksson, AL, Esko, T, Faul, JD, Ford, I, Forrester, T, Gertow, K, Gigante, B, Glorioso, N, Gong, J, Grallert, H, Grammer, TB, Grarup, N, Haitjema, S, Hallmans, G, Hamsten, A, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, ND, Heath, AC, Hernandez, D, Hindorff, L, Hocking, LJ, Hollensted, M, Holmen, OL, Homuth, G, Hottenga, JJ, Huang, J, Hung, J, Hutri-Kahonen, N, Ingelsson, E, James, AL, Jansson, JO, Jarvelin, MR, Jhun, MA, Jorgensen, ME, Juonala, M, Kahonen, M, Karlsson, M, Koistinen, HA, Kolcic, I, Kolovou, G, Kooperberg, C, Kramer, BK, Kuusisto, J, Kvaloy, K, Lakka, TA, Langenberg, C, Launer, LJ, Leander, K, Lee, NR, Lind, L, Lindgren, CM, Linneberg, A, Lobbens, S, Loh, M, Lorentzon, M, Luben, R, Lubke, G, Ludolph-Donislawski, A, Lupoli, S, Madden, PAF, Mannikko, R, Marques-Vidal, P, Martin, NG, McKenzie, CA, McKnight, B, Mellstrom, D, Menni, C, Montgomery, GW, Musk, AW, Narisu, N, Nauck, M, Nolte, IM, Oldehinkel, AJ, Olden, M, Ong, KK, Padmanabhan, S, Peyser, PA, Pisinger, C, Porteous, DJ, Raitakari, OT, Rankinen, T, Rao, DC, Rasmussen-Torvik, LJ, Rawal, R, Rice, T, Ridker, PM, Rose, LM, Bien, SA, Rudan, I, Sanna, S, Sarzynski, MA, Sattar, N, Savonen, K, Schlessinger, D, Scholtens, s, Schurmann, C, Scott, RA, Sennblad, B, Siemelink, MA, Silbernagel, G, Slagboom, PE (Eline), Snieder, H, Staessen, JA, Stott, DJ, Swertz, MA, Swift, AJ, Taylor, KD, Tayo, BO, Thorand, B, Thuillier, D, Tuomilehto, J, Uitterlinden, André, Vandenput, L, Vohl, MC, Volzke, H, Vonk, JM, Waeber, G, Waldenberger, M, Westendorp, RGJ, Wild, S, Willemsen, G, Wolffenbuttel, BHR, Wong, A, Wright, AF, Zhao, W, Zillikens, M.C., Baldassarre, D, Balkau, B, Bandinelli, S, Boger, CA, Boomsma, DI, Bouchard, C, Bruinenberg, M, Chasman, DI, Chen, YDI, Chines, PS, Cooper, RS, Cucca, F, Cusi, D, de Faire, U, Ferrucci, L, Franks, PW, Froguel, P, Gordon-Larsen, P, Grabe, HJ, Gudnason, V, Haiman, CA, Hayward, C, Hveem, K, Johnson, AD, Jukema, W, Kardia, SLR, Kivimaki, M, Kooner, JS, Kuh, D, Laakso, M, Lehtimaki, T, Le Marchand, L, Marz, W, McCarthy, MI, Metspalu, A, Morris, AP, Ohlsson, C, Palmer, LJ, Pasterkamp, G, Pedersen, O, Peters, A, Peters, U, Polasek, O, Psaty, BM, Qi, L, Rauramaa, R, Smith, BH, Sorensen, TIA, Strauch, K, Tiemeier, Henning, Tremoli, E, van der Harst, P, Vestergaard, H, Vollenweider, P, Wareham, NJ, Weir, DR, Whitfield, JB, Wilson, JF, Tyrrell, J, Frayling, TM, Barroso, I, Boehnke, M, Deloukas, P, Fox, CS, Hirschhorn, JN, Hunter, DJ, Spector, TD, Strachan, DP, Duijn, Cornelia, Heid, IM, Mohlke, KL, Marchini, J, Loos, RJF, Kilpelainen, TO, Liu, CT, Borecki, IB, North, KE, and Cupples, LA

Published
2017

40. Perception and Vaccination Status of Elderly Individuals Aged 60 Years and Above: An Urban Lahore Analysis

Author

Rizwana Kitchlew, Afaq Shamim, Spenta Kakalia, Arous Khaqan, Sonia Latif, and Faizan Farooq

Subjects
awareness, elderly, influenza, pakistan, pneumonia, vaccination, Medicine
Abstract

Introduction: Although there have been successful global efforts to provide vaccinations to children, immunization of the elderly has remained a largely neglected issue. There is currently no literature looking at vaccine coverage amongst the elderly in Pakistan. Worldwide, there is insufficient vaccine coverage among older adults, a group at high risk of acquiring vaccine preventable diseases. Aims & Objectives: Our objective was to assess vaccination status among the elderly in Pakistan, and reasons for being unvaccinated. Place and duration of study: The study was carried out at the Fatima Memorial Hospital, Lahore, Pakistan from 1st January 2019 till October 2019. Material & Methods: A cross-sectional analytical study was carried out on people over 60 years. Unvaccinated participants were counseled about the importance of vaccines, and for those willing, vaccination was arranged. Statistical analysis was carried out using SPSS version 23. Results: The 402 participants enrolled, 288(72%) knew that vaccinations can prevent diseases. Only 168(42%) were sure they had received any vaccine as an adult; the vaccine most often received was against hepatitis B, 84(21%). Influenza and pneumococcal vaccine had been received by 72(18%) and 44(11%), respectively. A large number of participants were completely unaware of the need for adult vaccines (38%), 16% had never been told about vaccinations by their primary care professional and 60% responded that there was not enough awareness regarding vaccination. There was a positive correlation between vaccination and education, along with social status (p

Published
2022
Full Text
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42. CSF rhinorrhoea after endonasal intervention to the skull base (CRANIAL): A multicentre prospective observational study

Author

CRANIAL Consortium, Danyal Z Khan, Hani J Marcus, Soham Bandyopadhyay, Benjamin E Schroeder, Vikesh Patel, Alice O’Donnell, Neurology and Neurosurgery Interest Group, British Neurosurgical Trainee Research Collaborative, Anastasios Giamouriadis, Pragnesh Bhatt, Bhaskar Ram, Adithya Varma, Philip Weir, Brendan Hanna, Theodore C Hirst, Patrick McAleavey, Alessandro Paluzzi, Georgios Tsermoulas, Shahzada Ahmed, Wai Cheong Soon, Yasir Arafat Chowdhury, Suhaib Abualsaud, Shumail Mahmood, Paresh Naik, Zohra Haiderkhan, Rafid Al-Mahfoudh, Andrea Perera, Mircea Rus, Adam Williams, Charles Hand, Kumar Abhinav, Cristina Cernei, Aiman Dilnawaz, Richard Mannion, Thomas Santarius, James Tysome, Rishi Sharma, Angelos G Kolias, Neil Donnelly, Ashwin Venkatesh, Caroline Hayhurst, Amr Mohamed, Benjamin Stew, Joseph Merola, Setthasorn Zhi Yang Ooi, Mahmoud Kamel, Mohammad Habibullah Khan, Sahibzada Abrar, Christopher Mckeon, Daniel McSweeney, Mohsen Javadpour, Peter Lacy, Daniel Murray, Elena Roman, Kismet Hossain-Ibrahim, Peter Ross, David Bennett, Nathan McSorley, Adam Hounat, Patrick Statham, Mark Hughes, Alhafidz Hamdan, Caroline Scott, Jigi Moudgil-Joshi, Anuj Bahl, Anna Bjornson, Daniel Gatt, Nick Phillips, Neeraj Kalra, Melissa Bautista, Seerat Shirazi, Catherine E Gilkes, Christopher P Millward, Ahmad MS Ali, Dimitris Paraskevopoulos, Jarnail Bal, Samir Matloob, Rhannon Lobo, Nigel Mendoza, Ramesh Nair, Arthur Dalton, Adarsh Nadig, Lucas Hernandez, Nick Thomas, Eleni Maratos, Jonathan Shapey, Sinan Al-Barazi, Asfand Baig Mirza, Mohamed Okasha, Prabhjot Singh Malhotra, Razna Ahmed, Neil L Dorward, Joan Grieve, Parag Sayal, David Choi, Ivan Cabrilo, Hugo Layard Horsfall, Jonathan Pollock, Alireza Shoakazemi, Oscar Maccormac, Guru N K Amirthalingam, Andrew Martin, Simon Stapleton, Florence Hogg, Daniel Richardson, Kanna Gnanalingham, Omar Pathmanaban, Daniel M Fountain, Raj Bhalla, Cathal J Hannan, Annabel Chadwick, Alistair Jenkins, Claire Nicholson, Syed Shumon, Mohamed Youssef, Callum Allison, Graham Dow, Iain Robertson, Laurence Johann Glancz, Murugan Sitaraman, Ashwin Kumaria, Ananyo Bagchi, Simon Cudlip, Jane Halliday, Rory J Piper, Alexandros Boukas, Meriem Amarouche, Damjan Veljanoski, Samiul Muquit, Ellie Edlmann, Haritha Maripi, Yi Wang, Mehnaz Hossain, Andrew Alalade, Syed Maroof, Pradnya Patkar, Saurabh Sinha, Showkat Mirza, Duncan Henderson, Mohammad Saud Khan, Nijaguna Mathad, Jonathan Hempenstall, Difei Wang, Department of Neurosurgery, Pavan Marwaha, Simon Shaw, Georgios Solomou, Alina Shrestha, Andrew Fraser, Theodore Hirst, Yasir Chowdhury, Sobiya Bilal, Jack Wildman, Priya Babu, Cian Carey, Renitha Reddi Bathuni, Joseph Nathaniel Brennan, Howra Ktayen, Sandhya T Trichinopoly, Danyal Khan, Seun Sobawale, Amir Suliman, Rory Piper, Will Owen, Afaq Sartaj, Edward Goacher, Euan Strachan, and Giorgios Solomou

Subjects
cerebrospinal fluid rhinorrhoea, CSF, EEA, endoscopic endonasal, cerebrospinal fluid leak, skull base surgery, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

ObjectiveDespite progress in endonasal skull-base neurosurgery, cerebrospinal fluid (CSF) rhinorrhoea remains common and significant. The CRANIAL study sought to determine 1) the scope of skull-base repair methods used, and 2) corresponding rates of postoperative CSF rhinorrhoea in the endonasal transsphenoidal approach (TSA) and the expanded endonasal approach (EEA) for skull-base tumors.MethodsA prospective observational cohort study of 30 centres performing endonasal skull-base neurosurgery in the UK and Ireland (representing 91% of adult units). Patients were identified for 6 months and followed up for 6 months. Data collection and analysis was guided by our published protocol and pilot studies. Descriptive statistics, univariate and multivariable logistic regression models were used for analysis.ResultsA total of 866 patients were included - 726 TSA (84%) and 140 EEA (16%). There was significant heterogeneity in repair protocols across centres. In TSA cases, nasal packing (519/726, 72%), tissue glues (474/726, 65%) and hemostatic agents (439/726, 61%) were the most common skull base repair techniques. Comparatively, pedicled flaps (90/140, 64%), CSF diversion (38/140, 27%), buttresses (17/140, 12%) and gasket sealing (11/140, 9%) were more commonly used in EEA cases. CSF rhinorrhoea (biochemically confirmed or requiring re-operation) occurred in 3.9% of TSA (28/726) and 7.1% of EEA (10/140) cases. A significant number of patients with CSF rhinorrhoea (15/38, 39%) occurred when no intraoperative CSF leak was reported. On multivariate analysis, there may be marginal benefits with using tissue glues in TSA (OR: 0.2, CI: 0.1-0.7, p

Published
2023
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43. The South Asian genome

Author

Chambers, JC, Abbott, J, Zhang, W, Turro, E, Scott, WR, Tan, ST, Afzal, U, Afaq, S, Loh, M, Lehne, B, O'Reilly, P, Gaulton, KJ, Pearson, RD, Li, X, Lavery, A, Vandrovcova, J, Wass, MN, Miller, K, Sehmi, J, Oozageer, L, Kooner, IK, Al-Hussaini, A, Mills, R, Grewal, J, Panoulas, V, Lewin, AM, Northwood, K, Wander, GS, Geoghegan, F, Li, Y, Wang, J, Aitman, TJ, McCarthy, MI, Scott, J, Butcher, S, Elliott, P, Kooner, JS, and Zhi, Degui

Subjects
Spatial Epidemiology, Epidemiology, lcsh:Medicine, Population genetics, Genome-wide association study, Human genetic variation, Cardiovascular, Genome, South Asians, Medicine and Health Sciences, 2.1 Biological and endogenous factors, DNA sequencing, Aetiology, lcsh:Science, Genetics of disease, Genetics, education.field_of_study, Multidisciplinary, Diabetes, Genomics, Single Nucleotide, 3. Good health, Asians, Research Design, Genetic Epidemiology, Sequence Analysis, Research Article, Human, Biotechnology, Asian Continental Ancestry Group, Asia, Genotype, Clinical Research Design, General Science & Technology, 1.1 Normal biological development and functioning, European Continental Ancestry Group, Population, Single-nucleotide polymorphism, Biology, Research and Analysis Methods, Polymorphism, Single Nucleotide, White People, Asian People, Clinical Research, Underpinning research, Genetic variation, Humans, Polymorphism, Molecular Biology Techniques, Sequencing Techniques, education, Molecular Biology, Alleles, Metabolic and endocrine, Whole genome sequencing, Population Biology, Genome, Human, Whites, lcsh:R, Human Genome, Biology and Life Sciences, Computational Biology, Genetic Variation, Sequence Analysis, DNA, DNA, Genome analysis, Genome Analysis, Genetics, Population, lcsh:Q, Genome-Wide Association Study
Abstract

Genetics of disease Microarrays Variant genotypes Population genetics Sequence alignment Alleles The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians. Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers).

Published
2014

45. Incidence, Clinicopathological Profile and Location - Based Outcome of Intracranial Meningiomas: 10-Year Institutional Study with Review of Literature

Author

Feroze Ganai, Humam Nisar Tanki, Afaq Sherwani, Kirmani Altaf, Nazish Chisti, and Altaf Ramzan

Subjects
intracranial lesions, meningioma, outcome meningioma, Surgery, RD1-811, Neurology. Diseases of the nervous system, RC346-429
Abstract

Intracranial meningiomas are the most common extra-axial tumors, representing 15% of all brain tumors. Arising from the arachnoid cells, and common in middle-aged women, 90% meningiomas are benign. We conducted a 10-year study on 183 cases of intracranial meningiomas and observed a lower and decreasing trend; the mean age was 43.3 years but there was also a significant incidence in young females. Parasagittal/falx (29%), sphenoid ridge, convexity meningiomas and middle cranial fossa locations were more common. Histopathologically, meningothelial meningioma was the most common. Benign (WHO I) tumors were found in above 90%, atypical (WHO II) in 5% cases, and malignant (WHO III) in < 4% patients. Most patients underwent Simpsons Grade I excision (35.6%) with dural reconstruction because of late presentations. Posterior fossa meningiomas were mostly benign, while intraventricular ones were mostly malignant with highest postoperation mortality. Mortality in operated patients was 9.8% but was highest in anterior fossa tumors (12.5%).

Published
2021
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47. Template-free synthesis of Se-nanorods-rGO nanocomposite for application in supercapacitors

Author

Ghouri Zafar Khan, Motlak Moaaed, Afaq Shagufta, Barakat Nasser A. M., and Abdala Ahmed

Subjects
nanorods, pseudocapacitor, selenium, graphene oxide, nanocomposites, Technology, Chemical technology, TP1-1185, Physical and theoretical chemistry, QD450-801
Abstract

Both selenium and reduced graphene oxide have low specific capacitance due to their chemical nature. Nevertheless, their specific capacitance could be enhanced by hybridizing Se nanomaterials with reduced graphene oxide via formation of electrochemical double layer at their interfacial area. Therefore, novel Se-nanorods/rGO nanocomposite was successfully synthesized by template free hot reflux route starting with graphene oxide and selenium dichloride. The composite of rGO decorated by Se-nanorods is characterized using X-ray diffractometry (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption– desorption. The unique architecture of the composite exhibits high specific capacitance of 390 F/ g at 5 mV/s scan rate in 1.0 M KOH solution with ~ 90% cyclic stability after 5000 cycles making it very promising electrode material for supercapacitor applications.

Published
2019
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48. Cycle Time Reduction in Injection Molding Process by Selection of Robust Cooling Channel Design.

Author

Khan, Muhammad, Afaq, S. Kamran, Khan, Nizar Ullah, and Ahmad, Saboor

Subjects
*MECHANICAL engineering, *MOLDING (Founding), *TEMPERATURE distribution, *ENERGY dissipation, *COOLING systems, *ROBUST control
Abstract

Cycle time of a part in injection molding process is very important as the rate of production and the quality of the parts produced depend on it, whereas the cycle time of a part can be reduced by reducing the cooling time which can only be achieved by the uniform temperature distribution in the molded part which helps in quick dissipation of heat. Conformal cooling channel design is the solution to the problem which basically "conforms" to the shape of cavity in the molds. This paper describes the analytical study of cooling analysis of different types of cooling channel designs. The best cooling channel design is also selected on the basis of minimum time to reach ejection temperature, uniform temperature distribution, and minimum warpage of part. "Creo Elements/Pro 5.0" is used to model the case study, its molds, and the cooling circuit whereas analytical study is done using "Autodesk Moldflow Advisor 2013 (AMFA)." [ABSTRACT FROM AUTHOR]

Published
2014
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49. Response of Black Nightshade (Solanum nigrum L.) to Phosphorus Application.

Author

Khan, M. M. A., Samiullah, Afaq, S. H., and Afridi, R. M.

Subjects
SOLANUM nigrum, PHOSPHORUS
Abstract

A pot experiment was conducted to study the effect of phosphorus (P) on the vegetative and reproductive growth of black nightshade (Solanum nigrum L.). Single superphosphate was applied at 0, 0.15, 0.30, 0.45, 0.60 and 0.75 g P/pot containing 3.5 kg of soil. Seeds were sown directly in pots and plant samples were taken at fortnightly intervals for recording growth and yield parameters. In addition, the solasodine content in fruit and N, P and K levels in leaves were also estimated. Most parameters were significantly influenced by P, with0.45 g/pot generally proving optimal. The data also established that the berries should be harvested between 160 and 190 days (days after sowing), preferably at 175 days for maximum fruit yield and solasodine production. Most parameters showed consistent and positive correlations with leaf P content. Interestingly, the correlation between leaf P content at 40 days and solasodine yield at 175 days was highly significant (r = 0.888), implying that the former is predictive of the latter. Thus, if low leaf P content was noted at 40 days corrective measures like foliar application or top dressing may be adopted to increase the leaf P content to ensure maximum solasodine at harvest. [ABSTRACT FROM AUTHOR]

Published
2000
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50. Response of Black Nightshade (Solarium nigrum L.) to Nitrogen Application.

Author

Khan, M. M. A., Samiullah, Afaq, S. H., and Afridi, R. M.

Subjects
SOLANUM nigrum, NITROGEN, SEEDS, LEAVES, SOLANUM
Abstract

Copyright of Journal of Agronomy & Crop Science is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
1995
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