Displaying publications 1 - 20 of 38 in total

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  1. Zheng Y, Lamoureux E, Finkelstein E, Wu R, Lavanya R, Chua D, et al.
    Invest Ophthalmol Vis Sci, 2011;52(12):8799-805.
    PMID: 21969296 DOI: 10.1167/iovs.11-7700
    It is known that a person's socioeconomic status (SES; individual-level SES) is closely correlated with his or her degree of visual impairment. Whether there is an independent relationship between area-level measures of SES (e.g., living in a lower SES environment) and visual impairment is unclear. This study describes the associations of area-level SES with visual impairment.
  2. Wu HM, Seet B, Yap EP, Saw SM, Lim TH, Chia KS
    Optom Vis Sci, 2001 Apr;78(4):234-9.
    PMID: 11349931
    PURPOSE: To study interethnic variation in myopia prevalence and severity in young adult males in Singapore and to determine whether these variations are related to differences in education level.

    METHODS: A population-based survey of refractive errors in a cohort of 15,095 military conscripts between July 1996 and June 1997 using noncycloplegic autorefraction and a standard questionnaire. Prevalence rates of myopia (

  3. Vithana EN, Aung T, Khor CC, Cornes BK, Tay WT, Sim X, et al.
    Hum Mol Genet, 2011 Feb 15;20(4):649-58.
    PMID: 21098505 DOI: 10.1093/hmg/ddq511
    Central corneal thickness (CCT) is a risk factor of glaucoma, the most common cause of irreversible blindness worldwide. The identification of genetic determinants affecting CCT in the normal population will provide insights into the mechanisms underlying the association between CCT and glaucoma, as well as the pathogenesis of glaucoma itself. We conducted two genome-wide association studies for CCT in 5080 individuals drawn from two ethnic populations in Singapore (2538 Indian and 2542 Malays) and identified novel genetic loci significantly associated with CCT (COL8A2 rs96067, p(meta) = 5.40 × 10⁻¹³, interval of RXRA-COL5A1 rs1536478, p(meta) = 3.05 × 10⁻⁹). We confirmed the involvement of a previously reported gene for CCT and brittle cornea syndrome (ZNF469) [rs9938149 (p(meta) = 1.63 × 10⁻¹⁶) and rs12447690 (p(meta) = 1.92 × 10⁻¹⁴)]. Evidence of association exceeding the formal threshold for genome-wide significance was observed at rs7044529, an SNP located within COL5A1 when data from this study (n = 5080, P = 0.0012) were considered together with all published data (reflecting an additional 7349 individuals, p(Fisher) = 1.5 × 10⁻⁹). These findings implicate the involvement of collagen genes influencing CCT and thus, possibly the pathogenesis of glaucoma.
  4. Vithana EN, Khor CC, Qiao C, Nongpiur ME, George R, Chen LJ, et al.
    Nat Genet, 2012 Oct;44(10):1142-1146.
    PMID: 22922875 DOI: 10.1038/ng.2390
    Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.
  5. Verkicharla PK, Ramamurthy D, Nguyen QD, Zhang X, Pu SH, Malhotra R, et al.
    Transl Vis Sci Technol, 2017 Jun;6(3):20.
    PMID: 28660095 DOI: 10.1167/tvst.6.3.20
    PURPOSE: To develop a fitness tracker (FitSight) to encourage children to increase time spent outdoors. To evaluate the wear pattern for this tracker and outdoor time pattern by estimating light illumination levels among children.

    METHODS: The development of the FitSight fitness tracker involved the designing of two components: (1) the smartwatch with custom-made FitSight watch application (app) to log the instant light illuminance levels the wearer is exposed to, and (2) a companion smartphone app that synchronizes the time outdoors recorded by the smartwatch to smartphone via Bluetooth communication. Smartwatch wear patterns and tracker-recorded daily light illuminance levels data were gathered over 7 days from 23 Singapore children (mean ± standard deviation age: 9.2 ± 1.4 years). Feedback about the tracker was obtained from 14 parents using a three-level rating scale: very poor/poor/good.

    RESULTS: Of the 14 parents, 93% rated the complete "FitSight fitness tracker" as good and 64% rated its wearability as good. While 61% of 23 children wore the watch on all study days (i.e., 0 nonwear days), 26% had 1 nonwear day, and 4.5% children each had 3, 4, and 5 nonwear days, respectively. On average, children spent approximately 1 hour in light levels greater than 1000 lux on weekdays and 1.3 hours on weekends (60 ± 46 vs. 79 ± 53 minutes, P = 0.19). Mean number of outdoor "spurts" (light illuminance levels >1000 lux) per day was 8 ± 3 spurts with spurt duration of 34 ± 32 minutes.

    CONCLUSION: The FitSight tracker with its novel features may motivate children to increase time outdoors and play an important role in supplementing community outdoor programs to prevent myopia.

    TRANSLATIONAL RELEVANCE: If the developed noninvasive, wearable, smartwatch-based fitness tracker, FitSight, promotes daytime outdoor activity among children, it will be beneficial in addressing the epidemic of myopia.

  6. Venketasubramanian N, Tan LC, Sahadevan S, Chin JJ, Krishnamoorthy ES, Hong CY, et al.
    Stroke, 2005 Mar;36(3):551-6.
    PMID: 15692124
    Stroke prevalence data among mixed Asian populations are lacking. Prevalence rates of stroke were studied among Singaporeans aged > or =50 years of Chinese, Malay, and Indian origin.
  7. Tan LC, Venketasubramanian N, Hong CY, Sahadevan S, Chin JJ, Krishnamoorthy ES, et al.
    Neurology, 2004 Jun 08;62(11):1999-2004.
    PMID: 15184604
    OBJECTIVE: To investigate the prevalence of Parkinson disease (PD) in Singapore and compare the rates between Singaporean Chinese, Malays, and Indians.

    METHODS: A three-phase community-based survey among a disproportionate random sample of 15,000 individuals (9,000 Chinese, 3,000 Malays, 3,000 Indians) aged 50 years and above who live in central Singapore was conducted. In phase 1, trained interviewers conducted a door-to-door survey using a validated 10-question questionnaire. In phase 2, medical specialists examined participants who screened positive to any of the questions. Participants suspected to have PD had their diagnosis confirmed in phase 3 by a movement disorders specialist.

    RESULTS: The participation rate was 67% among 22,279 eligible individuals. Forty-six participants with PD were identified of which 16 were newly diagnosed cases. The prevalence rate of PD for those aged 50 and above in Singapore was 0.30% (95% CI: 0.22 to 0.41), age-adjusted to US 1970 census. The prevalence rates increased significantly with age. The age-adjusted prevalence rates among Chinese (0.33%, 95% CI: 0.22 to 0.48), Malays (0.29%, 95% CI: 0.13 to 0.67), and Indians (0.28%, 95% CI: 0.12 to 0.67) were the same (p = 1.0).

    CONCLUSIONS: The prevalence of PD in Singapore was comparable to that of Western countries. Race-specific rates were also similar to previously reported rates and similar among the three races. Environmental factors may be more important than racially determined genetic factors in the development of PD.

  8. Tan JT, Ng DP, Nurbaya S, Ye S, Lim XL, Leong H, et al.
    J Clin Endocrinol Metab, 2010 Jan;95(1):390-7.
    PMID: 19892838 DOI: 10.1210/jc.2009-0688
    CONTEXT:
    Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized.

    OBJECTIVE:
    To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore.

    DESIGN:
    We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians.

    RESULTS:
    In Chinese, SNPs in CDKAL1 [odds ratio (OR) = 1.19; P = 2 x 10(-4)], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 x 10(-4)) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 x 10(-4)), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19-1.25; P = 0.003-2.5 x 10(-4)) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 x 10(-4)), CDKN2A/B (OR = 1.16; P = 9 x 10(-5)), HHEX (OR = 1.14; P = 6 x 10(-4)), and KCNQ1 (OR = 1.16-1.20; P = 3 x 10(-4) to 3 x 10(-6)) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry.

    CONCLUSIONS:
    SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.
  9. Tai ES, Sim XL, Ong TH, Wong TY, Saw SM, Aung T, et al.
    J Lipid Res, 2009 Mar;50(3):514-520.
    PMID: 18987386 DOI: 10.1194/jlr.M800456-JLR200
    We conducted a cross-sectional study of Malay participants aged 40-80 years (n = 2,932) to examine the associations between polymorphisms at newly identified, lipid-associated loci with blood lipid levels and prevalent cardiovascular disease (CVD) in a Malay population in Asia. A polymorphism adjacent to the TRIB1 locus (rs17321515) was associated with elevated total cholesterol and LDL-cholesterol (LDL-C) after adjustment for age and sex (both P values <0.007) and with increased risk of coronary heart disease and CVD [odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.03-1.46; and OR 1.2, 95% CI 1.02-1.42, respectively] under an additive model of inheritance. In addition, using recessive models of inheritance, polymorphisms on chromosome 19 adjacent to the CILP2 and PBX4 loci (rs16996148) and on chromosome 1 at the GALNT2 locus (rs4846914) were associated with elevated HDL-C (P = 0.005) and lower LDL-C (P = 0.048), respectively. Although novel, the former is consistent with the association between this polymorphism and lower blood triglycerides observed in the initial studies conducted in populations of European ancestry. Neither showed statistically significant association with CVD. These observations should form the basis of further investigation to identify the causative polymorphisms at this locus, and also to understand the mechanistic roles that this protein may play in lipoprotein metabolism in Asians and other populations.
  10. Sun C, Liew G, Wang JJ, Mitchell P, Saw SM, Aung T, et al.
    Invest Ophthalmol Vis Sci, 2008 May;49(5):1784-90.
    PMID: 18436813 DOI: 10.1167/iovs.07-1450
    To describe the relationship of retinal vascular caliber with cardiovascular risk factors in an Asian population.
  11. Soh SE, Chong YS, Kwek K, Saw SM, Meaney MJ, Gluckman PD, et al.
    Ann Nutr Metab, 2014;64(3-4):218-25.
    PMID: 25300263 DOI: 10.1159/000365023
    BACKGROUND: The dramatic emergence of noncommunicable diseases (NCD) in Asia, albeit with ethnic variation, has coincided with the rapid socioeconomic and nutritional transition taking place in the region, with the prevalence of diabetes rising 5-fold in Singapore in less than 4 decades. The Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study recruited 1,247 expectant mothers of Chinese, Malay, or Indian ethnicity in their first trimester, with detailed longitudinal tracking--through the antenatal period, birth, and the child's first 4 years of life--to examine the potential roles of fetal, developmental, and epigenetic factors in early pathways to metabolic and neurodevelopmental outcomes.

    KEY MESSAGES: A number of findings with a translational and clinical focus have already emerged. In the mothers, we found that changes and differences in food consumption varied across ethnic groups, with persistence of traditional beliefs, during pregnancy and the postpartum period. During pregnancy, higher maternal glucose levels, even in the absence of gestational diabetes mellitus, had graded relations with infant adiposity. Relations between maternal emotional health and birth outcomes and neurodevelopment have been identified. Genotype (25%) and in particular gene × environment interactions (75%) shape interindividual variations in the DNA methylome at birth. The complex effects of fixed genetic variations and different in utero environments can influence the epigenetic status at birth and the later-life phenotype.

    CONCLUSIONS: The richness of the clinical data in 3 ethnicities, the extent of the biospecimen collection, and the extensive infancy and preschool follow-up have allowed us to study the biological pathways that link fetal development to health outcomes. In the coming years, more sophisticated analyses of epigenotype-phenotype relationships will become possible as the children grow and develop. Our studies will lead to the development of clinical and population-based interventions to reduce the burden of NCD.

  12. Saw SM, Goh PP, Cheng A, Shankar A, Tan DT, Ellwein LB
    Br J Ophthalmol, 2006 Oct;90(10):1230-5.
    PMID: 16809384
    To compare the prevalences of refractive errors in Malay, Chinese and Indian children in Malaysia and Singapore.
  13. Sahadevan S, Saw SM, Gao W, Tan LC, Chin JJ, Hong CY, et al.
    J Am Geriatr Soc, 2008 Nov;56(11):2061-8.
    PMID: 19016940 DOI: 10.1111/j.1532-5415.2008.01992.x
    To study the prevalence of dementia in Singapore among Chinese, Malays, and Indians.
  14. Pang WW, Aris IM, Fok D, Soh SE, Chua MC, Lim SB, et al.
    Birth, 2016 Mar;43(1):68-77.
    PMID: 26643773 DOI: 10.1111/birt.12206
    BACKGROUND: Many countries in Asia report low breastfeeding rates and the risk factors for early weaning are not well studied. We assessed the prevalence, duration, and mode of breastfeeding (direct or expressed) among mothers of three Asian ethnic groups.

    METHODS: Participants were 1,030 Singaporean women recruited during early pregnancy. Data collected included early breastfeeding experiences, breastfeeding duration, and mode of breastfeeding. Full breastfeeding was defined as the intake of breast milk, with or without water. Cox regression models were used to identify factors associated with discontinuation of any and full breastfeeding. Logistic regression analyses assessed the association of ethnicity with mode of breastfeeding.

    RESULTS: At 6 months postpartum, the prevalence of any breastfeeding was 46 percent for Chinese mothers, 22 percent for Malay mothers, and 41 percent for Indian mothers; prevalence of full breastfeeding was 11, 2, and 5 percent, respectively. More Chinese mothers fed their infants expressed breast milk, instead of directly breastfeeding them, compared with the other two ethnic groups. Duration of any and full breastfeeding were positively associated with breastfeeding a few hours after birth, higher maternal age and education, and negatively associated with irregular breastfeeding frequency and being shown how to breastfeed. Adjusting for maternal education, breastfeeding duration was similar in the three ethnic groups, but ethnicity remained a significant predictor of mode of breastfeeding.

    CONCLUSIONS: The low rates and duration of breastfeeding in this population may be improved with breastfeeding education and support, especially in mothers with lower education. Further work is needed to understand the cultural differences in mode of feeding and its implications for maternal and infant health.

  15. Nongpiur ME, Khor CC, Jia H, Cornes BK, Chen LJ, Qiao C, et al.
    PLoS Genet, 2014 Mar;10(3):e1004089.
    PMID: 24603532 DOI: 10.1371/journal.pgen.1004089
    Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.
  16. Loon SC, Tay WT, Saw SM, Wang JJ, Wong TY
    Clin Exp Ophthalmol, 2009 May;37(4):362-7.
    PMID: 19594562 DOI: 10.1111/j.1442-9071.2009.02035.x
    To describe the prevalence and risk factors of ocular trauma in an urban Asian population.
  17. Loh FH, Khin LW, Saw SM, Lee JJ, Gu K
    Maturitas, 2005 Nov-Dec;52(3-4):169-80.
    PMID: 16257608
    To describe the prevalence of menopausal symptoms, define the mean age of menopause, and determine contributory factors, which influence the experience of symptoms among Singaporean women of different racial groups.
  18. Lim WY, Kwek K, Chong YS, Lee YS, Yap F, Chan YH, et al.
    J Hypertens, 2014 Apr;32(4):857-64.
    PMID: 24390251 DOI: 10.1097/HJH.0000000000000096
    OBJECTIVE: Greater maternal adiposity is a potentially modifiable risk factor for elevated blood pressure during pregnancy; however, the association has been little studied in Asian populations, and no study has evaluated potential differences in the adiposity-blood pressure relation between ethnic groups or interaction with gestational diabetes.

    METHODS: We performed a cross-sectional evaluation of a Singapore mother-offspring cohort comprising 799 pregnant Chinese, Malay and Indian women. Data on body weight, height, skinfold thickness and glycaemia (oral glucose tolerance test) were collected during the 2nd trimester; peripheral SBP and DBP were measured using an oscillometric device and central pressures by noninvasive radial applanation tonometry. The associations between adiposity measures BMI and sum of skinfold thickness and blood pressure outcomes were examined by linear regression with adjustment for potential confounders.

    RESULTS: Higher maternal BMI was associated with elevated peripheral and central pressures: the increases in pressure (mmHg) for each kg/m(2) increase in BMI were 1.19 (95% confidence interval, 1.03-1.36) for peripheral SBP, 0.76 (0.63-0.89) for peripheral DBP, 1.02 (0.87-1.17) for central systolic pressure and 0.26 (0.16-0.37) for central pulse pressure. The associations were generally stronger in Chinese women (P-interaction = 0.03 for central pulse pressure) and individuals with gestational diabetes (P-interaction = 0.03 for DBP and P-interaction = 0.046 for central systolic pressure). Similar patterns of results were found when using skinfold thickness as the measure of adiposity.

    CONCLUSION: Maternal adiposity is associated with higher peripheral and central blood pressures during pregnancy. Stronger associations in Chinese women and individuals with gestational diabetes warrant further investigation.
  19. Li Z, Allingham RR, Nakano M, Jia L, Chen Y, Ikeda Y, et al.
    Hum Mol Genet, 2015 Jul 01;24(13):3880-92.
    PMID: 25861811 DOI: 10.1093/hmg/ddv128
    Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.
  20. Lee YS, Kek BL, Poh LK, Saw SM, Loke KY
    J Pediatr Gastroenterol Nutr, 2008 Aug;47(2):172-8.
    PMID: 18664869 DOI: 10.1097/MPG.0b013e318162a0e5
    To identify factors associated with raised alanine transaminase, aspartate transaminase, and gamma-glutaryl transferase in severely obese children
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