RESULTS: We analyzed the whole-genome deep sequencing data (~ 30×) of five native trios from Peninsular Malaysia and North Borneo, and characterized the genomic variants, including single nucleotide variants (SNVs), small insertions and deletions (indels) and copy number variants (CNVs). We discovered approximately 6.9 million SNVs, 1.2 million indels, and 9000 CNVs in the 15 samples, of which 2.7% SNVs, 2.3% indels and 22% CNVs were novel, implying the insufficient coverage of population diversity in existing databases. We identified a higher proportion of novel variants in the Orang Asli (OA) samples, i.e., the indigenous people from Peninsular Malaysia, than that of the North Bornean (NB) samples, likely due to more complex demographic history and long-time isolation of the OA groups. We used the pedigree information to identify de novo variants and estimated the autosomal mutation rates to be 0.81 × 10- 8 - 1.33 × 10- 8, 1.0 × 10- 9 - 2.9 × 10- 9, and ~ 0.001 per site per generation for SNVs, indels, and CNVs, respectively. The trio-genomes also allowed for haplotype phasing with high accuracy, which serves as references to the future genomic studies of OA and NB populations. In addition, high-frequency inherited CNVs specific to OA or NB were identified. One example is a 50-kb duplication in DEFA1B detected only in the Negrito trios, implying plausible effects on host defense against the exposure of diverse microbial in tropical rainforest environment of these hunter-gatherers. The CNVs shared between OA and NB groups were much fewer than those specific to each group. Nevertheless, we identified a 142-kb duplication in AMY1A in all the 15 samples, and this gene is associated with the high-starch diet. Moreover, novel insertions shared with archaic hominids were identified in our samples.
CONCLUSION: Our study presents a full catalogue of the genome variants of the native Malaysian populations, which is a complement of the genome diversity in Southeast Asians. It implies specific population history of the native inhabitants, and demonstrated the necessity of more genome sequencing efforts on the multi-ethnic native groups of Malaysia and Southeast Asia.
DESIGN: Population-based incidence study using data from a medical savings fund.
STUDY POPULATION: Chinese, Malay, and Indian residents in Singapore.
METHODS: Data on all cataract operations performed for "senile cataract" (International Classification of Diseases, Ninth Revision, Clinical Modification code 366.1) between 1991 and 1996 were retrieved from Medisave, a population-wide, government-administered medical savings fund. The Singapore census was used as a denominator to allow an estimation of age, sex, and race-specific annual rates of cataract surgery.
RESULTS: Between 1991 and 1996, 61 210 cataract operations for "senile cataract" were performed on Singapore residents, which is equivalent to an average rate of 356.4 cataract operations per 100 000 persons per year (95% confidence interval [CI], 353.6-359.2). The average rate was highest for Indians (age-sex adjusted rate of 396.5 per 100 000/year), followed by Chinese (371.2 per 100 000/year), and lowest for Malays (237.2 per 100 000/year). Women had higher rates of cataract extraction than men (age-adjusted relative risk, 1.14; 95% CI, 1.11-1.17), with this pattern consistent across the 3 racial groups. The rate of cataract extraction increased by an average of 40 operations per 100 000/year (95% CI, 28.6-52.8) between 1991 and 1996. Overall, the proportion of cataract extraction without concurrent intraocular lens implantation was low (n = 762, 1.2%), but rates still decreased by an average of 0.8 per 100 000 per year (95% CI, 0.03-1.5) during the 6 years.
CONCLUSIONS: The rate of cataract extraction in Singapore is consistent with rates seen in developed countries in the West. Racial variation in rates suggests varying predisposition to cataract development and/or threshold for cataract surgery between Chinese, Malay, and Indian populations in Singapore.
DESIGN: Prospective, population cohort study.
PARTICIPANTS: The Singapore Malay Eye Study baseline participants (age, ≥40 years; 2006-2008) were followed up in 2011 through 2013, and 1901 of 3280 of eligible participants (72.1%) took part.
METHODS: Fundus photographs were graded using the Wisconsin AMD grading system.
MAIN OUTCOME MEASURES: Incidence of early and late AMD.
RESULTS: Gradable fundus photographs were available for 1809 participants who attended both baseline and 6-year follow-up examinations. The age-standardized incidences of early and late AMD were 5.89% (95% confidence interval [CI], 4.81-7.16) and 0.76% (95% CI, 0.42-1.29), respectively. The 5-year age-standardized incidence of early AMD (calculated based on the 6-year incidence) was lower in our population (5.58%; 95% CI, 4.43-7.01) compared with the Beaver Dam Eye Study population (8.19%). The incidence of late AMD in our population was similar to that of the Beaver Dam Eye Study population (0.98% [95% CI, 0.49-1.86] vs. 0.91%), the Blue Mountains Eye Study population (1.10% [95% CI, 0.52-9.56] vs. 1.10%), and the Hisayama Study population (1.09% [95% CI, 0.54-4.25] vs. 0.84%). The incidence of late AMD increased markedly with increasing baseline AREDS score (step 0, 0.23%; step 4, 9.09%).
CONCLUSIONS: This study documented the incidence of early and late AMD in a Malay population. The AREDS simplified severity scale is useful in predicting the risk of late AMD development in Asians.