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147 results on '"Karnani, Neerja"'

1. A Catalogue of Structural Variation across Ancestrally Diverse Asian Genomes

Author

Tan, Joanna Hui Juan, Li, Zhihui, Porta, Mar Gonzalez, Rajaby, Ramesh, Lim, Weng Khong, Tan, Ye An, Jimenez, Rodrigo Toro, Teo, Renyi, Hebrard, Maxime, Ow, Jack Ling, Ang, Shimin, Jeyakani, Justin, Chong, Yap Seng, Lim, Tock Han, Goh, Liuh Ling, Tham, Yih Chung, Leong, Khai Pang, Chin, Calvin Woon Loong, Davila, Sonia, Karnani, Neerja, Cheng, Ching-Yu, Chambers, John, Tai, E. Shyong, Liu, Jianjun, Sim, Xueling, Sung, Wing Kin, Prabhakar, Shyam, Tan, Patrick, and Bertin, Nicolas

Published
2024
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2. Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia

Author

Membrez, Mathieu, Migliavacca, Eugenia, Christen, Stefan, Yaku, Keisuke, Trieu, Jennifer, Lee, Alaina K., Morandini, Francesco, Giner, Maria Pilar, Stiner, Jade, Makarov, Mikhail V., Garratt, Emma S., Vasiloglou, Maria F., Chanvillard, Lucie, Dalbram, Emilie, Ehrlich, Amy M., Sanchez-Garcia, José Luis, Canto, Carles, Karagounis, Leonidas G., Treebak, Jonas T., Migaud, Marie E., Heshmat, Ramin, Razi, Farideh, Karnani, Neerja, Ostovar, Afshin, Farzadfar, Farshad, Tay, Stacey K. H., Sanders, Matthew J., Lillycrop, Karen A., Godfrey, Keith M., Nakagawa, Takashi, Moco, Sofia, Koopman, René, Lynch, Gordon S., Sorrentino, Vincenzo, and Feige, Jerome N.

Published
2024
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3. Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk: a preconception and longitudinal cohort study

Author

Chen, Li, Mir, Sartaj Ahmad, Bendt, Anne K., Chua, Esther W. L., Narasimhan, Kothandaraman, Tan, Karen Mei-Ling, Loy, See Ling, Tan, Kok Hian, Shek, Lynette P., Chan, Jerry, Yap, Fabian, Meaney, Michael J., Chan, Shiao-Yng, Chong, Yap Seng, Gluckman, Peter D., Eriksson, Johan G., Karnani, Neerja, and Wenk, Markus R.

Published
2023
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4. The Singapore National Precision Medicine Strategy

Author

Wong, Eleanor, Bertin, Nicolas, Hebrard, Maxime, Tirado-Magallanes, Roberto, Bellis, Claire, Lim, Weng Khong, Chua, Chee Yong, Tong, Philomena Mei Lin, Chua, Raymond, Mak, Kenneth, Lim, Tit Meng, Cheong, Wei Yang, Thien, Kwee Eng, Goh, Khean Teik, Chai, Jin-Fang, Lee, Jimmy, Sung, Joseph Jao-Yiu, Wong, Tien Yin, Chin, Calvin Woon Loong, Gluckman, Peter D., Goh, Liuh Ling, Ban, Kenneth Hon Kim, Tan, Tin Wee, Sim, Xueling, Cheng, Ching-Yu, Davila, Sonia, Karnani, Neerja, Leong, Khai Pang, Liu, Jianjun, Prabhakar, Shyam, Maurer-Stroh, Sebastian, Verma, Chandra Shekhar, Krishnaswamy, Pavitra, Goh, Rick Siow Mong, Chia, Irenaeus, Ho, Clarissa, Low, Doreen, Virabhak, Suchin, Yong, Jacklyn, Zheng, Weiling, Seow, Shih Wee, Seck, Yee Kwang, Koh, Mingshi, Chambers, John C., Tai, E. Shyong, and Tan, Patrick

Published
2023
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5. Time-to-conception and clinical pregnancy rate with a myo-inositol, probiotics, and micronutrient supplement: secondary outcomes of the NiPPeR randomized trial

Author

Albert, Ben, Cai, Shirong, Calder, Philip C., Carvalho, Ryan, Guiao Castro, Julie Ann, Cavanagh, Mary, Chan, Jerry KY., Chang, Mei Ling, Chi, Claudia, Childs, Caroline E., Choh, Mei Kit, Chong, Mary FF., Chu, Anne HY., Conlon, Cathryn, Paula Costello, Cyrus Cooper, Cox, Vanessa, Galani, Sevasti, Hammond, Judith, Harvey, Nicholas C., Holt, Richard, Inskip, Hazel M., Jagtap, Mrunalini, Jeon, Gene, Karnani, Neerja, Nembrini, Chiara, Lillycrop, Karen A., Müller-Riemenschneider, Falk, Natarajan, Padmapriya, Ng, Sharon, Ramasamy, Adaikalavan, Tham, Elizabeth, Tint, Mya Thway, O’Sullivan, Justin M., Satianegara, Gernalia, Shek, Lynette PC., Silva-Zolezzi, Irma, Sim, Wendy, Soh, Shu E., Tay, Vicky, Taylor, Rachel, Theodosia, Salika, Wall, Clare, Woon, Gladys, Vickers, Mark, Ying, Wei, Chan, Shiao-Yng, Barton, Sheila J., Loy, See Ling, Chang, Hsin Fang, Titcombe, Philip, Wong, Jui-Tsung, Ebreo, Marilou, Ong, Judith, Tan, Karen ML., Nield, Heidi, El-Heis, Sarah, Kenealy, Timothy, Chong, Yap-Seng, Baker, Philip N., Cutfield, Wayne S., and Godfrey, Keith M.

Published
2023
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6. A five-safes approach to a secure and scalable genomics data repository

Author

Shih, Chih Chuan, Chen, Jieqi, Lee, Ai Shan, Bertin, Nicolas, Hebrard, Maxime, Khor, Chiea Chuen, Li, Zheng, Juan Tan, Joanna Hui, Meah, Wee Yang, Peh, Su Qin, Mok, Shi Qi, Sim, Kar Seng, Liu, Jianjun, Wang, Ling, Wong, Eleanor, Li, Jingmei, Tin, Aung, Cheng, Ching-Yu, Heng, Chew-Kiat, Yuan, Jian-Min, Koh, Woon-Puay, Saw, Seang Mei, Friedlander, Yechiel, Sim, Xueling, Chai, Jin Fang, Chong, Yap Seng, Davila, Sonia, Goh, Liuh Ling, Lee, Eng Sing, Wong, Tien Yin, Karnani, Neerja, Leong, Khai Pang, Yeo, Khung Keong, Chambers, John C., Lim, Su Chi, Goh, Rick Siow Mong, Tan, Patrick, and Dorajoo, Rajkumar

Published
2023
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7. Breastfeeding may benefit cardiometabolic health of children exposed to increased gestational glycemia in utero

Author

Ong, Yi Ying, Pang, Wei Wei, Huang, Jonathan Y., Aris, Izzuddin M., Sadananthan, Suresh Anand, Tint, Mya-Thway, Yuan, Wen Lun, Chen, Ling-Wei, Chan, Yiong Huak, Karnani, Neerja, Velan, S. Sendhil, Fortier, Marielle V., Choo, Jonathan, Ling, Lieng Hsi, Shek, Lynette, Tan, Kok Hian, Gluckman, Peter D., Yap, Fabian, Chong, Yap-Seng, Godfrey, Keith M., Chong, Mary F-F., Chan, Shiao-Yng, Eriksson, Johan G., Wlodek, Mary E., Lee, Yung Seng, and Michael, Navin

Published
2022
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10. The socioeconomic landscape of the exposome during pregnancy

Author

Sum, Ka Kei, Tint, Mya Thway, Aguilera, Rosana, Dickens, Borame Sue Lee, Choo, Sue, Ang, Li Ting, Phua, Desiree, Law, Evelyn C., Ng, Sharon, Tan, Karen Mei-Ling, Benmarhnia, Tarik, Karnani, Neerja, Eriksson, Johan G., Chong, Yap-Seng, Yap, Fabian, Tan, Kok Hian, Lee, Yung Seng, Chan, Shiao-Yng, Chong, Mary F.F., and Huang, Jonathan

Published
2022
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13. Population-based plasma lipidomics reveals developmental changes in metabolism and signatures of obesity risk: a mother-offspring cohort study

Author

Mir, Sartaj Ahmad, Chen, Li, Burugupalli, Satvika, Burla, Bo, Ji, Shanshan, Smith, Adam Alexander T., Narasimhan, Kothandaraman, Ramasamy, Adaikalavan, Tan, Karen Mei-Ling, Huynh, Kevin, Giles, Corey, Mei, Ding, Wong, Gerard, Yap, Fabian, Tan, Kok Hian, Collier, Fiona, Saffery, Richard, Vuillermin, Peter, Bendt, Anne K., Burgner, David, Ponsonby, Anne-Louise, Lee, Yung Seng, Chong, Yap Seng, Gluckman, Peter D., Eriksson, Johan G., Meikle, Peter J., Wenk, Markus R., and Karnani, Neerja

Published
2022
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14. Analysis of clinically relevant variants from ancestrally diverse Asian genomes

Author

Chan, Sock Hoai, Bylstra, Yasmin, Teo, Jing Xian, Kuan, Jyn Ling, Bertin, Nicolas, Gonzalez-Porta, Mar, Hebrard, Maxime, Tirado-Magallanes, Roberto, Tan, Joanna Hui Juan, Jeyakani, Justin, Li, Zhihui, Chai, Jin Fang, Chong, Yap Seng, Davila, Sonia, Goh, Liuh Ling, Lee, Eng Sing, Wong, Eleanor, Wong, Tien Yin, Prabhakar, Shyam, Liu, Jianjun, Cheng, Ching-Yu, Eisenhaber, Birgit, Karnani, Neerja, Leong, Khai Pang, Sim, Xueling, Yeo, Khung Keong, Chambers, John C., Tai, E-Shyong, Tan, Patrick, Jamuar, Saumya S., Ngeow, Joanne, and Lim, Weng Khong

Published
2022
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16. The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells

Author

McEwen, Lisa M., O’Donnell, Kieran J., McGill, Megan G., Edgar, Rachel D., Jones, Meaghan J., MacIsaac, Julia L., Lin, David Tse Shen, Ramadori, Katia, Morin, Alexander, Gladish, Nicole, Garg, Elika, Unternaehrer, Eva, Pokhvisneva, Irina, Karnani, Neerja, Kee, Michelle Z. L., Klengel, Torsten, Adler, Nancy E., Barr, Ronald G., Letourneau, Nicole, Giesbrecht, Gerald F., Reynold, James N., Czamara, Darina, Armstrong, Jeffrey M., Essex, Marilyn J., de Weerth, Carolina, Beijers, Roseriet, Tollenaar, Marieke S., Bradley, Bekh, Jovanovic, Tanja, Ressler, Kerry J., Steiner, Meir, Entringer, Sonja, Wadhwa, Pathik D., Buss, Claudia, Bush, Nicole R., Binder, Elisabeth B., Boyce, Thomas, Meaney, Michael J., Horvath, Steve, and Kobor, Michael S.

Published
2020

18. High placental inositol content associated with suppressed pro-adipogenic effects of maternal glycaemia in offspring: the GUSTO cohort

Author

Chu, Anne H. Y., Tint, Mya T., Chang, Hsin F., Wong, Gerard, Yuan, Wen Lun, Tull, Dedreia, Nijagal, Brunda, Narayana, Vinod K., Meikle, Peter J., Chang, Kenneth T. E., Lewis, Rohan M., Chi, Claudia, Yap, Fabian K. P., Tan, Kok Hian, Shek, Lynette P., Chong, Yap-Seng, Gluckman, Peter D., Lee, Yung Seng, Fortier, Marielle V., Godfrey, Keith M., Eriksson, Johan G., Karnani, Neerja, and Chan, Shiao-Yng

Published
2021
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20. Determinants of intramyocellular lipid accumulation in early childhood

Author

Michael, Navin, Gupta, Varsha, Sadananthan, Suresh Anand, Sampathkumar, Aparna, Chen, Li, Pan, Hong, Tint, Mya Thway, Lee, Kuan Jin, Loy, See Ling, Aris, Izzuddin M., Shek, Lynette Pei-Chi, Yap, Fabian Kok Peng, Godfrey, Keith M., Leow, Melvin K.-S., Lee, Yung Seng, Kramer, Michael S., Henry, Christiani Jeyakumar, Fortier, Marielle Valerie, Seng Chong, Yap, Gluckman, Peter D., Karnani, Neerja, and Velan, S. Sendhil

Published
2020
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22. The placental lipidome of maternal antenatal depression predicts socio-emotional problems in the offspring

Author

Wong, Gerard, Weir, Jacquelyn M., Mishra, Priti, Huynh, Kevin, Nijagal, Brunda, Gupta, Varsha, Broekman, Birit F. P., Chong, Mary Foong-Fong, Chan, Shiao-Yng, Tan, Kok Hian, Tull, Dedreia, McConville, Malcolm, Calder, Philip C., Godfrey, Keith M., Chong, Yap Seng, Gluckman, Peter D., Meaney, Michael J., Meikle, Peter J., and Karnani, Neerja

Published
2021
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25. Temporal Profile of Replication of Human Chromosomes

Author

Jeon, Yesu, Bekiranov, Stefan, Karnani, Neerja, Kapranov, Philipp, Ghosh, Srinka, MacAlpine, David, Lee, Charles, Hwang, Deog Su, Gingeras, Thomas R., Dutta, Anindya, and Kelly, Thomas J.

Published
2005

27. Umbilical Cord Plasma Lysophospholipids and Triacylglycerols Associated with Birthweight Percentiles.

Author

Wong, Gerard, Narasimhan, Kothandaraman, Cheong, Wei Fun, Ng, Sharon, Aris, Izzuddin M., Loy, See Ling, Bendt, Anne K., Tan, Kok Hian, Yap, Fabian K. P., Shek, Lynette P., Chong, Yap Seng, Gluckman, Peter D., Godfrey, Keith M., Lee, Yung Seng, Wenk, Markus R., Karnani, Neerja, and Chan, Shiao-Yng

Abstract

Dysregulated transplacental lipid transfer and fetal–placental lipid metabolism affect birthweight, as does maternal hyperglycemia. As the mechanisms are unclear, we aimed to identify the lipids in umbilical cord plasma that were most associated with birthweight. Seventy-five Chinese women with singleton pregnancies recruited into the GUSTO mother–offspring cohort were selected from across the glycemic range based on a mid-gestation 75 g oral glucose tolerance test, excluding pre-existing diabetes. Cord plasma samples collected at term delivery were analyzed using targeted liquid-chromatography tandem mass-spectrometry to determine the concentrations of 404 lipid species across 17 lipid classes. The birthweights were standardized for sex and gestational age by local references, and regression analyses were adjusted for the maternal age, BMI, parity, mode of delivery, insulin treatment, and fasting/2 h glucose, with a false discovery-corrected p < 0.05 considered significant. Ten lysophosphatidylcholines (LPCs) and two lysophosphatidylethanolamines were positively associated with the birthweight percentiles, while twenty-four triacylglycerols were negatively associated with the birthweight percentiles. The topmost associated lipid was LPC 20:2 [21.28 (95%CI 12.70, 29.87) percentile increase in the standardized birthweight with each SD-unit increase in log10-transformed concentration]. Within these same regression models, maternal glycemia did not significantly associate with the birthweight percentiles. Specific fetal circulating lysophospholipids and triacylglycerols associate with birthweight independently of maternal glycemia, but a causal relationship remains to be established. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities

Author

Migliavacca, Eugenia, Tay, Stacey K. H., Patel, Harnish P., Sonntag, Tanja, Civiletto, Gabriele, McFarlane, Craig, Forrester, Terence, Barton, Sheila J., Leow, Melvin K., Antoun, Elie, Charpagne, Aline, Seng Chong, Yap, Descombes, Patrick, Feng, Lei, Francis-Emmanuel, Patrice, Garratt, Emma S., Giner, Maria Pilar, Green, Curtis O., Karaz, Sonia, Kothandaraman, Narasimhan, Marquis, Julien, Metairon, Sylviane, Moco, Sofia, Nelson, Gail, Ngo, Sherry, Pleasants, Tony, Raymond, Frederic, Sayer, Avan A., Ming Sim, Chu, Slater-Jefferies, Jo, Syddall, Holly E., Fang Tan, Pei, Titcombe, Philip, Vaz, Candida, Westbury, Leo D., Wong, Gerard, Yonghui, Wu, Cooper, Cyrus, Sheppard, Allan, Godfrey, Keith M., Lillycrop, Karen A., Karnani, Neerja, and Feige, Jerome N.

Published
2019
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31. Multigenerational adversity impacts on human gut microbiome composition and socioemotional functioning in early childhood.

Author

Querdasi, Francesca R., Enders, Craig, Karnani, Neerja, Broekman, Birit, Chong Yap Seng, Gluckman, Peter D., Daniel, Lourdes Mary, Yap, Fabian, Eriksson, Johan G., Shirong Cai, Mary Foong-Fong Chong, Jia Ying Toh, Godfrey, Keith, Meaney, Michael J., and Callaghan, Bridget L.

Subjects
GUT microbiome, HUMAN microbiota, CHILD mental health services, LIFE change events, CHILD abuse, ADULT child abuse victims, PUERPERIUM
Abstract

Adversity exposures in the prenatal and postnatal period are associated with an increased risk for psychopathology, which can be perpetuated across generations. Nonhuman animal research highlights the gut microbiome as a putative biological mechanism underlying such generational risks. In a sample of 450 mother–child dyads living in Singapore, we examined associations between three distinct adversity exposures experienced across two generations—maternal childhood maltreatment, maternal prenatal anxiety, and second-generation children’s exposure to stressful life events—and the gut microbiome composition of second-generation children at 2 y of age. We found distinct differences in gut microbiome profiles linked to each adversity exposure, as well as some nonaffected microbiome features (e.g., beta diversity). Remarkably, some of the microbial taxa associated with concurrent and prospective child socioemotional functioning shared overlapping putative functions with those affected by adversity, suggesting that the intergenerational transmission of adversity may have a lasting impact on children’s mental health via alterations to gut microbiome functions. Our findings open up a new avenue of research into the underlying mechanisms of intergenerational transmission of mental health risks and the potential of the gut microbiome as a target for intervention. [ABSTRACT FROM AUTHOR]

Published
2023
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32. DNA methylome variation in a perinatal nurse-visitation program that reduces child maltreatment: a 27-year follow-up

Author

O’Donnell, Kieran J., Chen, Li, MacIsaac, Julia L., McEwen, Lisa M., Nguyen, Thao, Beckmann, Katherine, Zhu, Yuecai, Chen, Lawrence Ming, Brooks-Gunn, Jeanne, Goldman, David, Grigorenko, Elena L., Leckman, James F., Diorio, Josie, Karnani, Neerja, Olds, David L., Holbrook, Joanna D., Kobor, Michael S., and Meaney, Michael J.

Published
2018
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33. Association of physical activity and sedentary behavior with depression and anxiety symptoms during pregnancy in a multiethnic cohort of Asian women

Author

Padmapriya, Natarajan, Bernard, Jonathan Y., Liang, Shen, Loy, See Ling, Shen, Zhe, Kwek, Kenneth, Godfrey, Keith M., Gluckman, Peter D., Chong, Yap-Seng, Saw, Seang Mei, Meaney, Michael J., Chen, Helen, Müller-Riemenschneider, Falk, Agarwal, Pratibha, Biswas, Arijit, Bong, Choon Looi, Broekman, Birit F. P., Cai, Shirong, Chan, Jerry Kok Yen, Chan, Yiong Huak, Chee, Cornelia Yin Ing, Cheung, Yin Bun, Chinnadurai, Amutha, Chng, Chai Kiat, Chong, Mary Foong-Fong, Chong, Shang Chee, Chua, Mei Chien, Fok, Doris, Fortier, Marielle V., Goh, Anne Eng Neo, Goh, Yam Thiam Daniel, Gooley, Joshua J., Han, Wee Meng, Hanson, Mark, Henry, Christiani Jeyakumar, Holbrook, Joanna D., Hsu, Chin-Ying, Karnani, Neerja, Kapur, Jeevesh, Lau, Ivy Yee-Man, Lee, Bee Wah, Lee, Yung Seng, Lek, Ngee, Lim, Sok Bee, Magiati, Iliana, Daniel, Lourdes Mary, Ngo, Cheryl, Niduvaje, Krishnamoorthy, Pang, Wei Wei, Qiu, Anqi, Quah, Boon Long, Rajadurai, Victor Samuel, Rauff, Mary, Rebello, Salome A., Richmond, Jenny L., Rifkin-Graboi, Anne, Shek, Lynette Pei-Chi, Sheppard, Allan, Shuter, Borys, Singh, Leher, Soh, Shu-E, Stunkel, Walter, Su, Lin Lin, Tan, Kok Hian, Teoh, Oon Hoe, Tint, Mya Thway, van Bever, Hugo P. S., van Dam, Rob M., Wong, Inez Bik Yun, Wong, P. C., Yap, Fabian, Yeo, George Seow Heong, and On behalf of the GUSTO Study Group

Published
2016
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35. Safety, Tolerability, and Pharmacokinetics of β-Cryptoxanthin Supplementation in Healthy Women: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Author

Tan, Karen M. L., Chee, Jolene, Lim, Kezlyn L. M., Ng, Maisie, Gong, Min, Xu, Jia, Tin, Felicia, Natarajan, Padmapriya, Lee, Bee Lan, Ong, Choon Nam, Tint, Mya Thway, Kee, Michelle Z. L., Müller-Riemenschneider, Falk, Gluckman, Peter D., Meaney, Michael J., Kumar, Mukkesh, Karnani, Neerja, Eriksson, Johan G., Nandanan, Bindu, and Wyss, Adrian

Abstract

Background: β-cryptoxanthin is a dietary carotenoid for which there have been few studies on the safety and pharmacokinetics following daily oral supplementation. Methods: 90 healthy Asian women between 21 and 35 years were randomized into three groups: 3 and 6 mg/day oral β-cryptoxanthin, and placebo. At 2, 4, and 8 weeks of supplementation, plasma carotenoid levels were measured. The effects of β-cryptoxanthin on blood retinoid-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition were investigated. Results: β-cryptoxanthin supplementation for 8 weeks (3 and 6 mg/day) was found to be safe and well tolerated. Plasma β-cryptoxanthin concentration was significantly higher in the 6 mg/day group (9.0 ± 4.1 µmol/L) compared to 3 mg/day group (6.0 ± 2.6 µmol/L) (p < 0.03), and placebo (0.4 ± 0.1 µmol/L) (p < 0.001) after 8 weeks. Plasma all-trans retinol, α-cryptoxanthin, α-carotene, β-carotene, lycopene, lutein, and zeaxanthin levels were not significantly changed. No effects were found on blood retinol-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition. Conclusions: Oral β-cryptoxanthin supplementation over 8 weeks lead to high plasma concentrations of β-cryptoxanthin, with no impact on other carotenoids, and was well tolerated in healthy women. [ABSTRACT FROM AUTHOR]

Published
2023
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36. Prenatal diet, plasma micronutrients/metabolome and inflammatory status influence the development of atopic eczema in early childhood.

Author

Ta, Le Duc Huy, Chan, James Chun Yip, Yap, Gaik Chin, Huang, Chiung‐Hui, Tham, Elizabeth Huiwen, Loo, Evelyn Xiu Ling, Suaini, Noor H. A., Shek, Lynette P., Karnani, Neerja, Goh, Anne Eng Neo, Van Bever, Hugo P. S., Teoh, Oon Hoe, Chan, Yiong Huak, Lay, Christophe, Knol, Jan, Yap, Fabian, Tan, Kok Hian, Chong, Yap‐Seng, Chong, Mary Foong‐Fong, and Chan, Shiao Yng

Subjects
ECZEMA, ATOPIC dermatitis, MICRONUTRIENTS, MACROPHAGE inflammatory proteins, DIET, TRANSFORMING growth factors-beta
Abstract

This maternal signature was associated with raised maternal C-reactive Protein (CRP) level, as well as increased pro-inflammatory markers in the infant cord blood (CRP, IL-6, IL-7, MIP3 , VEGF-A, and TGF 1) and trigonelline compared with non-eczema controls (Figure 1). Abbreviations CRP C-Reactive Protein IL Interleukin MIP3 Macrophage Inflammatory Protein-3 alpha TGF 1 Transforming growth factor beta 1 VEGF-A Vascular endothelial growth factor A Atopic eczema is one of the commonest chronic inflammatory skin disorders in childhood. [Extracted from the article]

Published
2023
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37. Profiling Microbial Communities in Idiopathic Granulomatous Mastitis.

Author

Ong, Seeu Si, Xu, Jia, Sim, Choon Kiat, Khng, Alexis Jiaying, Ho, Peh Joo, Kwan, Philip Kam Weng, Ravikrishnan, Aarthi, Tan, Kiat-Tee Benita, Tan, Qing Ting, Tan, Ern Yu, Tan, Su-Ming, Putti, Thomas Choudary, Lim, Swee Ho, Tang, Ee Ling Serene, Nagarajan, Niranjan, Karnani, Neerja, Li, Jingmei, and Hartman, Mikael

Subjects
MICROBIAL communities, MASTITIS, WILCOXON signed-rank test, MICROBIAL diversity, ETIOLOGY of diseases
Abstract

Idiopathic granulomatous mastitis (IGM) is a rare and benign inflammatory breast disease with ambiguous aetiology. Contrastingly, lactational mastitis (LM) is commonly diagnosed in breastfeeding women. To investigate IGM aetiology, we profiled the microbial flora of pus and skin in patients with IGM and LM. A total of 26 patients with IGM and 6 patients with LM were included in the study. The 16S rRNA sequencing libraries were constructed from 16S rRNA gene amplified from total DNA extracted from pus and skin swabs in patients with IGM and LM controls. Constructed libraries were multiplexed and paired-end sequenced on HiSeq4000. Metagenomic analysis was conducted using modified microbiome abundance analysis suite customised R-resource for paired pus and skin samples. Microbiome multivariable association analyses were performed using linear models. A total of 21 IGM and 3 LM paired pus and skin samples underwent metagenomic analysis. Bray−Curtis ecological dissimilarity distance showed dissimilarity across four sample types (IGM pus, IGM skin, LM pus, and LM skin; PERMANOVA, p < 0.001). No characteristic dominant genus was observed across the IGM samples. The IGM pus samples were more diverse than corresponding IGM skin samples (Shannon and Simpson index; Wilcoxon paired signed-rank tests, p = 0.022 and p = 0.07). Corynebacterium kroppenstedtii, reportedly associated with IGM in the literature, was higher in IGM pus samples than paired skin samples (Wilcoxon, p = 0.022). Three other species and nineteen genera were statistically significant in paired IGM pus–skin comparison after antibiotic treatment adjustment and multiple comparisons correction. Microbial profiles are unique between patients with IGM and LM. Inter-patient variability and polymicrobial IGM pus samples cannot implicate specific genus or species as an infectious cause for IGM. [ABSTRACT FROM AUTHOR]

Published
2023
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38. Timing of introduction of complementary foods, breastfeeding, and child cardiometabolic risk: a prospective multiethnic Asian cohort study.

Author

Yi Ying Ong, Wei Wei Pang, Michael, Navin, Aris, Izzuddin M., Sadananthan, Suresh Anand, Tint, Mya-Thway, Tze Liang Choo, Jonathan, Lieng Hsi Ling, Karnani, Neerja, Velan, S. Sendhil, Fortier, Marielle V., Kok Hian Tan, Gluckman, Peter D., Yap, Fabian, Yap-Seng Chong, Godfrey, Keith M., Shiao-Yng Chan, Eriksson, Johan G., Chong, Mary F.-F., and Wlodek, Mary E.

Subjects
METABOLIC syndrome risk factors, CARDIOVASCULAR diseases risk factors, MOTHERS, SKINFOLD thickness, CONFIDENCE intervals, TIME, CHILDHOOD obesity, INFANTS, SYSTOLIC blood pressure, MULTIPLE regression analysis, NUTRITIONAL requirements, INFANT nutrition, RISK assessment, DIASTOLIC blood pressure, BREASTFEEDING, METABOLIC syndrome, DESCRIPTIVE statistics, RESEARCH funding, BODY mass index, ADIPOSE tissues, LONGITUDINAL method, LIPIDS, DISEASE risk factors, CHILDREN
Abstract

Background: The timing of introduction of complementary foods and the duration of breastfeeding (BF) have been independently associated with child overweight and obesity; however, their combined influence on body fat partitioning and cardiometabolic risk is unclear. Objective: We investigated the associations of the timing of introduction of complementary foods, the duration of BF, and their interaction with child adiposity and cardiometabolic risk markers. Methods: We analyzed data from 839 children in the prospective Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Mothers reported the age at which infants were first fed complementary foods and BF duration, classified as early (≤4 mo) versus typical (>4 mo) complementary feeding (CF) and short (≤4 mo) versus long (>4 mo) duration of any BF, respectively. We measured adiposity and cardiometabolic risk markers at the age of 6 y and examined their associations with infant feeding patterns using multiple regression, adjusting for sociodemographics, parents' body mass index (BMI), maternal factors, birth weight for gestational age, and infant weight gain. Results: Of 839 children, 18% experienced early CF, whereas 54% experienced short BF. Short (vs. long) BF and early (vs. typical) CF were independently associated with higher z-scores of BMI [β (95% confidence interval), short BF, 0.18 standard deviation score (SDS) (-0.01, 0.38); early CF, 0.34 SDS (0.11, 0.57)] and sum of skinfolds [short BF, 1.83 mm (0.05, 3.61); early CF, 2.73 mm (0.55, 4.91)]. Children who experienced both early CF and short BF (vs. typical CF-long BF) had synergistically higher diastolic blood pressure [1.41 mmHg (-0.15, 2.97), P-interaction = 0.023] and metabolic syndrome score [0.81 (0.16, 1.47), P-interaction = 0.081]. Early CF-long BF (vs. early CF-short BF) was associated with a lower systolic blood pressure [-3.74 mmHg (-7.01, -0.48)], diastolic blood pressure [-2.29 mmHg (-4.47, -0.11)], and metabolic syndrome score [-0.90 (-1.80, 0.00)]. Conclusions: A combination of early CF and short BF was associated with elevated child adiposity and cardiometabolic markers. Longer BF duration may protect against cardiometabolic risk associated with early CF. This trial was registered at clinicaltrials.gov as NCT01174875. [ABSTRACT FROM AUTHOR]

Published
2023
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39. Associations of maternal and foetoplacental factors with prehypertension/hypertension in early childhood.

Author

Michael, Navin, Sadananthan, Suresh Anand, Yuan, Wen Lun, Ong, Yi Ying, Loy, See Ling, Huang, Jonathan Y., Tint, Mya-Thway, Padmapriya, Natarajan, Choo, Jonathan, Ling, Lieng Hsi, Kramer, Michael S., Godfrey, Keith M., Gluckman, Peter D., Tan, Kok Hian, Eriksson, Johan G., Chong, Yap-Seng, Lee, Yung Seng, Karnani, Neerja, Yap, Fabian, and Shek, Lynette Pei-Chi

Published
2022
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40. Genetic Link Determining the Maternal-Fetal Circulation of Vitamin D.

Author

Sampathkumar, Aparna, Tan, Karen M., Chen, Li, Chong, Mary F. F., Yap, Fabian, Godfrey, Keith M., Chong, Yap Seng, Gluckman, Peter D., Ramasamy, Adaikalavan, and Karnani, Neerja

Subjects
VITAMIN D, GENOME-wide association studies, GENETIC variation, MISSENSE mutation, SINGLE nucleotide polymorphisms, VITAMIN D deficiency
Abstract

Vitamin D is an essential micronutrient whose demand is heightened during pregnancy to support the growth of the fetus. Furthermore, the fetus does not produce vitamin D and hence relies exclusively on the supply of maternal vitamin D through the placenta. Vitamin D inadequacy is linked with pregnancy complications and adverse infant outcomes. Hence, early predictive markers of vitamin D inadequacy such as genetic vulnerability are important to both mother and offspring. In this multi-ethnic Asian birth cohort study, we report the first genome-wide association analysis (GWAS) of maternal and fetal vitamin D in circulation. For this, 25-hydroxyvitamin D (25OHD) was measured in the antenatal blood of mothers during mid gestation (n =942), and the cord blood of their offspring at birth (n =812). Around ~7 million single nucleotide polymorphisms (SNPs) were regressed against 25OHD concentrations to identify genetic risk variants. About 41% of mothers had inadequate 25OHD (≤75nmol/L) during pregnancy. Antenatal 25OHD was associated with ethnicity [Malay (Β =−22.32nmol/L, p =2.3×10−26); Indian (Β =−21.85, p =3.1×10−21); reference Chinese], age (Β =0.47/year, p =0.0058), and supplement intake (Β =16.47, p =2.4×10−13). Cord blood 25OHD highly correlated with antenatal vitamin D (r =0.75) and was associated with ethnicity [Malay (Β =−4.44, p =2.2×10−7); Indian (Β =−1.99, p =0.038); reference Chinese]. GWAS analysis identified rs4588, a missense variant in the group-specific component (GC) gene encoding vitamin D binding protein (VDBP), and its defining haplotype, as a risk factor for low antenatal (Β =−8.56/T-allele, p =1.0×10−9) and cord blood vitamin D (Β =−3.22/T-allele, p =1.0×10−8) in all three ethnicities. We also discovered a novel association in a SNP downstream of CYP2J2 (rs10789082), a gene involved in 25-hydroxylation of vitamin D, with vitamin D in pregnant women (Β =−7.68/G-allele, p =1.5×10−8), but not their offspring. As the prevention and early detection of suboptimal vitamin D levels are of profound importance to both mother and offspring's health, the genetic risk variants identified in this study allow risk assessment and precision in early intervention of vitamin D deficiency. [ABSTRACT FROM AUTHOR]

Published
2021
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41. Integrative multi-omics database (iMOMdb) of Asian pregnant women.

Author

Pan, Hong, Tan, Pei Fang, Lim, Ives Y, Huan, Jason, Teh, Ai Ling, Chen, Li, Gong, Min, Tin, Felicia, Mir, Sartaj Ahmad, Narasimhan, Kothandaraman, Chan, Jerry K Y, Tan, Kok Hian, Kobor, Michael S, Meikle, Peter J, Wenk, Markus R, Chong, Yap Seng, Eriksson, Johan G, Gluckman, Peter D, and Karnani, Neerja

Published
2022
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43. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project

Author

Birney, Ewan, Stamatoyannopoulos, John A., Dutta, Anindya, Guigo, Roderic, Gingeras, Thomas R., Margulies, Elliott H., Weng, Zhiping, Snyder, Michael, Dermitzakis, Emmanouil T., Thurman, Robert E., Kuehn, Michael S., Taylor, Christopher M., Neph, Shane, Koch, Christoph M., Asthana, Saurabh, Malhotra, Ankit, Adzhubei, Ivan, Greenbaum, Jason A., Andrews, Robert M., Flicek, Paul, Boyle, Patrick J., Cao, Hua, Carter, Nigel P., Clelland, Gayle K., Davis, Sean, Day, Nathan, Dhami, Pawandeep, Dillon, Shane C., Dorschner, Michael O., Fiegler, Heike, Giresi, Paul G., Goldy, Jeff, Hawrylycz, Michael, Haydock, Andrew, Humbert, Richard, James, Keith D., Johnson, Brett E., Johnson, Ericka M., Frum, Tristan T., Rosenzweig, Elizabeth R., Karnani, Neerja, Lee, Kirsten, Lefebvre, Gregory C., Navas, Patrick A., Neri, Fidencio, Parker, Stephen C. J., Sabo, Peter J., Sandstrom, Richard, Shafer, Anthony, Vetrie, David, Weaver, Molly, Wilcox, Sarah, Yu1, Man, Collins, Francis S., Dekker, Job, Lieb, Jason D., Tullius, Thomas D., Crawford, Gregory E., Sunyaev, Shamil, Noble, William S., Dunham, Ian, Denoeud, France, Reymond, Alexandre, Kapranov, Philipp, Rozowsky, Joel, Zheng, Deyou, Castelo, Robert, Frankish, Adam, Harrow, Jennifer, Ghosh, Srinka, Sandelin, Albin, Hofacker, Ivo L., Baertsch, Robert, Keefe, Damian, Dike, Sujit, Cheng, Jill, Hirsch, Heather A., Sekinger, Edward A., Lagarde, Julien, Abril, Josep F., Shahab, Atif, Flamm, Christoph, Fried, Claudia, Hackermuller, Jorg, Hertel, Jana, Lindemeyer, Manja, Missal, Kristin, Tanzer, Andrea, Washietl, Stefan, Korbel, Jan, Emanuelsson, Olof, Pedersen, Jakob S., Holroyd, Nancy, Taylor, Ruth, Swarbreck, David, Matthews, Nicholas, Dickson, Mark C., Thomas, Daryl J., Weirauch, Matthew T., Gilbert, James, Drenkow, Jorg, Bell, Ian, Zhao, XiaoDong, Srinivasan, K.G., Sung, Wing-Kin, Ooi, Hong Sain, Chiu, Kuo Ping, Foissac, Sylvain, Alioto, Tyler, Brent, Michael, Pachter, Lior, Tress, Michael L., Valencia, Alfonso, Choo, Siew Woh, Choo, Chiou Yu, Ucla, Catherine, Manzano, Caroline, Wyss, Carine, Cheung, Evelyn, Clark, Taane G., Brown, James B., Ganesh, Madhavan, Patel, Sandeep, Tammana, Hari, Chrast, Jacqueline, Henrichsen, Charlotte N., Kai, Chikatoshi, Kawai, Jun, Nagalakshmi, Ugrappa, Wu, Jiaqian, Lian, Zheng, Lian, Jin, Newburger, Peter, Zhang, Xueqing, Bickel, Peter, Mattick, John S., Carninci, Piero, Hayashizaki, Yoshihide, Weissman, Sherman, Hubbard, Tim, Myers, Richard M., Rogers, Jane, Stadler, Peter F., Lowe, Todd M., Wei, Chia-Lin, Ruan, Yijun, Struhl, Kevin, Gerstein, Mark, Antonarakis, Stylianos E., Fu, Yutao, Green, Eric D., Karaoz, Ulaş, Siepel, Adam, Taylor, James, Liefer, Laura A., Wetterstrand, Kris A., Good, Peter J., Feingold, Elise A., Guyer, Mark S., Cooper, Gregory M., Asimenos, George, Dewey, Colin N., Hou, Minmei, Nikolaev, Sergey, Montoya-Burgos, Juan I., Loytynoja, Ari, Whelan, Simon, Pardi, Fabio, Massingham, Tim, Huang, Haiyan, Zhang, Nancy R., Holmes, Ian, Mullikin, James C., Ureta-Vidal, Abel, Paten, Benedict, Seringhaus, Michael, Church, Deanna, Rosenbloom, Kate, Kent, W. James, Stone, Eric A., Batzoglou, Serafim, Goldman, Nick, Hardison, Ross C., Haussler, David, Miller, Webb, Sidow, Arend, Trinklein, Nathan D., Zhang, Zhengdong D., Barrera, Leah, Stuart, Rhona, King, David C., Ameur, Adam, Enroth, Stefan, Bieda, Mark C., Kim, Jonghwan, Bhinge, Akshay A., Jiang, Nan, Liu, Jun, Yao, Fei, Vega, Vinsensius B., Lee, Charlie W.H., Ng, Patrick, Yang, Annie, Moqtaderi, Zarmik, Zhu, Zhou, Xu, Xiaoqin, Squazzo, Sharon, Oberley, Matthew J., Inman, David, Singer, Michael A., Richmond, Todd A., Munn, Kyle J., Rada-Iglesias, Alvaro, Wallerman, Ola, Komorowski, Jan, Fowler, Joanna C., Couttet, Phillippe, Bruce, Alexander W., Dovey, Oliver M., Ellis, Peter D., Langford, Cordelia F., Nix, David A., Euskirchen, Ghia, Hartman, Stephen, Urban, Alexander E., Kraus, Peter, Van Calcar, Sara, Heintzman, Nate, Hoon Kim, Tae, Wang, Kun, Qu, Chunxu, Hon, Gary, Luna, Rosa, Glass, Christopher K., Rosenfeld, M. Geoff, Aldred, Shelley Force, Cooper, Sara J., Halees, Anason, Lin, Jane M., Shulha, Hennady P., Zhang, Xiaoling, Xu, Mousheng, Haidar, Jaafar N. S., Yu, Yong, Birney*, Ewan, Iyer, Vishwanath R., Green, Roland D., Wadelius, Claes, Farnham, Peggy J., Ren, Bing, Harte, Rachel A., Hinrichs, Angie S., Trumbower, Heather, Clawson, Hiram, Hillman-Jackson, Jennifer, Zweig, Ann S., Smith, Kayla, Thakkapallayil, Archana, Barber, Galt, Kuhn, Robert M., Karolchik, Donna, Armengol, Lluis, Bird, Christine P., de Bakker, Paul I. W., Kern, Andrew D., Lopez-Bigas, Nuria, Martin, Joel D., Stranger, Barbara E., Woodroffe, Abigail, Davydov, Eugene, Dimas, Antigone, Eyras, Eduardo, Hallgrimsdottir, Ingileif B., Huppert, Julian, Zody, Michael C., Abecasis, Goncalo R., Estivill, Xavier, Bouffard, Gerard G., Guan, Xiaobin, Hansen, Nancy F., Idol, Jacquelyn R., Maduro, Valerie V.B., Maskeri, Baishali, McDowell, Jennifer C., Park, Morgan, Thomas, Pamela J., Young, Alice C., Blakesley, Robert W., Baylor College of Medicine, Human Genome Sequencing Center, Muzny, Donna M., Sodergren, Erica, Wheeler, David A., Worley, Kim C., Jiang, Huaiyang, Weinstock, George M., Gibbs, Richard A., Graves, Tina, Fulton, Robert, Mardis, Elaine R., Wilson, Richard K., Clamp, Michele, Cuff, James, Gnerre, Sante, Jaffe, David B., Chang, Jean L., Lindblad-Toh, Kerstin, Lander, Eric S., Koriabine, Maxim, Nefedov, Mikhail, Osoegawa, Kazutoyo, Yoshinaga, Yuko, Zhu, Baoli, and de Jong, Pieter J.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): The ENCODE Project Consortium; Analysis Coordination; Ewan Birney (corresponding author) [1]; John A. Stamatoyannopoulos (corresponding author) [2]; Anindya Dutta (corresponding author) [3]; Roderic Guigó (corresponding author) [4, 5]; Thomas [...]

Published
2007
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45. Activated brown adipose tissue releases exosomes containing mitochondrial methylene tetrahydrofolate dehydrogenase (NADP dependent) 1-like protein (MTHFD1L).

Author

Leow, Melvin Khee-Shing, Rengaraj, Anantharaj, Narasimhan, Kothandaraman, Verma, Sanjay K., Yaligar, Jadegoud, Thi Thu, Giang Le, Sun, Lijuan, Hui Jen Goh, Govindharajulu, Priya, Sadananthan, Suresh Anand, Michael, Navin, Wei Meng, Gallart-Palau, Xavier, Lei Sun, Karnani, Neerja, Kwan Sze, Newman Siu, and Sendhil Velan, S.

Subjects
BROWN adipose tissue, TETRAHYDROFOLATE dehydrogenase, NICOTINAMIDE adenine dinucleotide phosphate, EXOSOMES, MITOCHONDRIAL proteins, IONIZING radiation, MALATE dehydrogenase
Abstract

Brown adipose tissue (BAT) is a promising weapon to combat obesity and metabolic disease. BAT is thermogenic and consumes substantial amounts of glucose and fatty acids as fuel for thermogenesis and energy expenditure. To study BAT function in large human longitudinal cohorts, safe and precise detection methodologies are needed. Although regarded a gold standard, the foray of PET-CT into BAT research and clinical applications is limited by its high ionizing radiation doses. Here, we show that brown adipocytes release exosomes in blood plasma that can be utilized to assess BAT activity. In the present study, we investigated circulating protein biomarkers that can accurately and reliably reflect BAT activation triggered by cold exposure, capsinoids ingestion and thyroid hormone excess in humans. We discovered an exosomal protein, methylene tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L), to be overexpressed and detectable in plasma for all three modes of BAT activation in human subjects. This mitochondrial protein is packaged as a cargo within multivesicular bodies of the endosomal compartment and secreted as exosomes via exocytosis from activated brown adipocytes into the circulation. To support MTHFD1L as a conserved BAT activation response in other vertebrates, we examined a rodent model and also proved its presence in blood of rats following BAT activation by cold exposure. Plasma concentration of exosomal MTHFD1L correlated with human BAT activity as confirmed by PET-MR in humans and supported by data from rats. Thus, we deduce that MTHFD1L appears to be overexpressed in activated BAT compared to BAT in the basal nonstimulated state. [ABSTRACT FROM AUTHOR]

Published
2022
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46. ANRIL Promoter DNA Methylation: A Perinatal Marker for Later Adiposity

Author

Lillycrop, Karen, Murray, Robert, Cheong, Clara, Teh, Ai Ling, Clarke-Harris, Rebecca, Barton, Sheila, Costello, Paula, Garratt, Emma, Cook, Eloise, Titcombe, Philip, Shunmuganathan, Bhuvaneshwari, Liew, Samantha J., Chua, Yong-Cai, Lin, Xinyi, Wu, Yonghui, Burdge, Graham C., Cooper, Cyrus, Inskip, Hazel M., Karnani, Neerja, Hopkins, James C., Childs, Caroline E., Chavez, Carolina Paras, Calder, Philip C., Yap, Fabian, Lee, Yung Seng, Chong, Yap Seng, Melton, Philip E., Beilin, Lawrie, Huang, Rae-Chi, Gluckman, Peter D., Harvey, Nick, Hanson, Mark A., Holbrook, Joanna D., Godfrey, Keith M., and Lee Kong Chian School of Medicine (LKCMedicine)

Subjects
Adult, Male, Adolescent, lcsh:Medicine, Epigenesis, Genetic, Young Adult, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p18, Humans, Science::Medicine [DRNTU], Obesity, Child, Promoter Regions, Genetic, Cyclin-Dependent Kinase Inhibitor p16, Aged, Adiposity, lcsh:R5-920, DNA methylation, lcsh:R, Infant, Newborn, Infant, Epigenetic, Middle Aged, DNA Methylation, CpG Islands, Female, RNA, Long Noncoding, lcsh:Medicine (General), Biomarkers, Research Paper
Abstract

Experimental studies show a substantial contribution of early life environment to obesity risk through epigenetic processes. We examined inter-individual DNA methylation differences in human birth tissues associated with child's adiposity. We identified a novel association between the level of CpG methylation at birth within the promoter of the long non-coding RNA ANRIL (encoded at CDKN2A) and childhood adiposity at age 6-years. An association between ANRIL methylation and adiposity was also observed in three additional populations; in birth tissues from ethnically diverse neonates, in peripheral blood from adolescents, and in adipose tissue from adults. Additionally, CpG methylation was associated with ANRIL expression in vivo, and CpG mutagenesis in vitro inhibited ANRIL promoter activity. Furthermore, CpG methylation enhanced binding to an Estrogen Response Element within the ANRIL promoter. Our findings demonstrate that perinatal methylation at loci relevant to gene function may be a robust marker of later adiposity, providing substantial support for epigenetic processes in mediating long-term consequences of early life environment on human health., Highlights • DNA methylation within the ANRIL promoter region was predictive of measures of adiposity in four independent cohorts. • DNA methylation may be a marker for late gestation fetal undernutrition, followed by rapid postnatal weight gain. • Altered DNA methylation associated with p16INK4a and p14ARF expression. • ERα may bind at the ANRIL promoter, and in vitro E2 treatment stimulated expression of ANRIL, while reducing p14 expression. The quality of the early life environment before birth can affect susceptibility to metabolic disease later in the lifecourse, with epigenetic regulation of gene function thought to be one mechanism through which early life environmental factors induce persistent phenotypic changes. In this study, using DNA from the Southampton Women's Survey (SWS), we identified changes in DNA methylation levels at birth that associated with adiposity later in childhood within the promoter of ANRIL, a gene with strong disease associations that is involved in regulatiing cellular growth. This finding was replicated in several independent cohorts, and functionally validated in adipocyte cells.

Published
2017

47. Ontogeny of circulating lipid metabolism in pregnancy and early childhood -- a longitudinal population study.

Author

Burugupalli, Satvika, Smith, Adam Alexander T., Oshlensky, Gavriel, Huynh, Kevin, Giles, Corey, Wang, Tingting, George, Alexandra, Paul, Sudip, Anh Nguyen, Thy Duong, Mellett, Natalie, Cinel, Michelle, Mir, Sartaj Ahmad, Li Chen, Wenk, Markus R., Karnani, Neerja, Collier, Fiona, Saffery, Richard, Vuillermin, Peter, and Ponsonby, Anne- Louise

Published
2022
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48. Dichotomy in the Impact of Elevated Maternal Glucose Levels on Neonatal Epigenome.

Author

Lim, Ives Yubin, Xinyi Lin, Ai Ling Teh, Yonghui Wu, Li Chen, He, Menglan, Shiao-Yng Chan, MacIsaac, Julia L., Chan, Jerry K. Y., Kok Hian Tan, Foong Fong Chong, Mary, Kobor, Michael S., Godfrey, Keith M., Meaney, Michael J., Yung Seng Lee, Eriksson, Johan G., Gluckman, Peter D., Yap Seng Chong, and Karnani, Neerja

Subjects
HYPERGLYCEMIA, GLYCEMIC control
Abstract

Context: Antenatal hyperglycemia is associated with increased risk of future adverse health outcomes in both mother and child. Variations in offspring's epigenome can reflect the impact and response to in utero glycemic exposure, and may have different consequences for the child. Objective: We examined possible differences in associations of basal glucose status and glucose handling during pregnancy with both clinical covariates and offspring cord tissue DNA methylation. Research Design and Methods: This study included 830 mother-offspring dyads from the Growing Up in Singapore Towards Healthy Outcomes cohort. The fetal epigenome of umbilical cord tissue was profiled using Illumina HumanMethylation450 arrays. Associations of maternal mid-pregnancy fasting (fasting plasma glucose [FPG]) and 2-hour plasma glucose (2hPG) after a 75-g oral glucose challenge with both maternal clinical phenotypes and offspring epigenome at delivery were investigated separately. Results: Maternal age, prepregnancy body mass index, and blood pressure measures were associated with both FPG and 2hPG, whereas Chinese ethnicity (P = 1.9 × 10-4), maternal height (P = 1.1 × 10-4), pregnancy weight gain (P = 2.2 × 10-3), prepregnancy alcohol consumption (P = 4.6 × 10-4), and tobacco exposure (P = 1.9 × 10-3) showed significantly opposite associations between the 2 glucose measures. Most importantly, we observed a dichotomy in the effects of these glycemic indices on the offspring epigenome. Offspring born to mothers with elevated 2hPG showed global hypomethylation. CpGs most associated with the 2 measures also reflected differences in gene ontologies and had different associations with offspring birthweight. Conclusions: Our findings suggest that 2 traditionally used glycemic indices for diagnosing gestational diabetes may reflect distinctive pathophysiologies in pregnancy, and have differential impacts on the offspring's DNA methylome. [ABSTRACT FROM AUTHOR]

Published
2022
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49. Association between early life weight gain and abdominal fat partitioning at 4.5 years is sex, ethnicity, and age dependent

Author

Sadananthan, Suresh Anand, Tint, Mya Thway, Michael, Navin, Aris, Izzuddin M., Loy, See Ling, Lee, Kuan Jin, Shek, Lynette Pei-Chi, Yap, Fabian Kok Peng, Tan, Kok Hian, Godfrey, Keith M., Leow, Melvin Khee-Shing, Lee, Yung Seng, Kramer, Michael S., Gluckman, Peter D., Chong, Yap Seng, Karnani, Neerja, Henry, Christiani Jeyakumar, Fortier, Marielle Valerie, Velan, S. Sendhil, and Lee Kong Chian School of Medicine (LKCMedicine)

Subjects
Medicine [Science], Weight Gain, Age, Gender and Race
Abstract

Objective: The aim of this study was to investigate the independent associations between age‐specific annual weight gain from birth to age 4 years and fat deposition in metabolically distinct compartments at age 4.5 years in a South Asian longitudinal birth cohort. Methods: Volumetric abdominal magnetic resonance imaging with comprehensive segmentation of deep and superficial subcutaneous adipose tissue (SAT) and visceral adipose tissues (VAT) was performed in 316 children (150 boys and 166 girls in three ethnic groups; 158 Chinese, 94 Malay, and 64 Indian) aged 4.5 years. Associations between fat volumes and annual relative weight gain conditional on past growth were assessed overall and stratified by sex and ethnicity. Results: Conditional relative weight gain had stronger associations with greater SAT and VAT at age 4.5 years in girls than boys and in Indians compared with Malay and Chinese. Overall, the magnitude of association was the largest during 2 to 3 years for SAT and 1 to 2 years for VAT. Despite similar body weight, Indian children and girls had the highest deep and superficial SAT volumes at age 4.5 years (all interactions P < 0.05). No significant sex or ethnic differences were observed in VAT. With increasing BMI, Indian children had the highest tendency to accumulate VAT, and girls accumulated more fat than boys in all depots (all interactions P < 0.001). Conclusions: Indian ethnicity and female sex predisposed children to accumulate more fat in the VAT depot with increasing conditional relative weight gain in the second year of life. Thus, 1 to 2 years of age may be a critical window for interventions to reduce visceral fat accumulation. Agency for Science, Technology and Research (A*STAR) Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, and Nestec. KMG is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (as a NIHR Senior Investigator [NF-SI-0515-10042] and through the NIHR Southampton Biomedical Research Centre), and the European Union’s Seventh Framework Programme (FP7/2007-2013), projects EarlyNutrition and ODIN, under grant agreement numbers 289346 and 613977.

Published
2019

50. Role of maternal tryptophan metabolism in allergic diseases in the offspring.

Author

Lau, Hui Xing, El‐Heis, Sarah, Yap, Qai Ven, Chan, Yiong Huak, Tan, Cheryl Pei Ting, Karnani, Neerja, Tan, Karen Mei Ling, Tham, Elizabeth Huiwen, Goh, Anne Eng Neo, Teoh, Oon Hoe, Tan, Kok Hian, Eriksson, Johan Gunnar, Chong, Yap Seng, Chong, Mary Foong‐Fong, Van Bever, Hugo, Lee, Bee Wah, Shek, Lynette P., Godfrey, Keith M., and Loo, Evelyn Xiu Ling

Subjects
WHEEZE, PEANUT allergy, TRYPTOPHAN, NICOTINAMIDE, ALLERGIES, METABOLISM, SKIN tests, INFANTS
Abstract

Background: Nicotinamide (vitamin B3) is a metabolite of tryptophan and dietary precursor of enzymes involved in many regulatory processes, which may influence fetal immune development. Objective: We examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with the risk of development of infant eczema, wheeze, rhinitis or allergic sensitization. Methods: In the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, we analysed the associations between maternal plasma levels of nicotinamide, tryptophan and tryptophan metabolites at 26–28 weeks of gestation and allergic outcomes collected through interviewer‐administered questionnaires at multiple time‐points and skin prick testing to egg, milk, peanut and mites at age 18 months. Multivariate analysis was undertaken adjusting for all metabolites measured and separately adjusting for relevant demographic and environmental exposures. Analyses were also adjusted for multiple comparisons using the false discovery method. Results: Tryptophan metabolites were evaluated in 976/1247 (78%) women enrolled in GUSTO. In multivariate analysis including all metabolites, maternal plasma 3‐hydrokynurenine was associated with increased allergic sensitization at 18 months (AdjRR 2.6, 95% CI 1.3–5.2 for highest quartile) but the association with nicotinamide was not significant (AdjRR 1.8, 95% CI 0.9–3.6). In analysis adjusting for other exposures, both 3‐hydrokynurenine and nicotinamide were associated with increased allergic sensitization (AdjRR 2.0, 95% CI 1.1–3.6 for both metabolites). High maternal plasma nicotinamide was associated with increased infant eczema diagnosis by 6 and 12 months, which was not significant when adjusting for all metabolites measured, but was significant when adjusting for relevant environmental and demographic exposures. Other metabolites measured were not associated with allergic sensitization or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze. Conclusions and Clinical Relevance: Maternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants. [ABSTRACT FROM AUTHOR]

Published
2021
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