RESUMEN
Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.
Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Exoma/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética , Metabolismo de los Lípidos/genética , Pueblo Asiatico/genética , Enfermedad de la Arteria Coronaria/etnología , Europa (Continente) , Asia Oriental , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/etnología , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Lípidos/análisis , Población Blanca/genéticaRESUMEN
STUDY OBJECTIVES: Previous cross-sectional studies showed that short or long sleep duration was associated with memory impairment (MI), but longitudinal studies are scarce. We examined whether sleep duration was associated with memory decline or development of MI. DESIGN SETTING PARTICIPANTS: We conducted a prospective analysis based on the Guangzhou Biobank Cohort Study on 13,888 participants aged 50+ years without MI at baseline and with a follow-up for a mean of 4.1 years. MEASURES AND RESULTS: Memory decline was assessed using the Delayed 10-Word Recall Test (DWRT), and in a subset (n = 6,020) with the Mini-Mental State Examination (MMSE). Short and long sleep duration was defined as ≤ 5 hours/day and ≥ 9 hours/day, respectively. Data were analyzed both continuously for memory decline and dichotomously for MI (independently defined as DWRT, < 4; MMSE, < 25). After adjusting for multiple potential confounders, both short and long sleep durations were associated with memory decline using DWRT or MMSE score changes (all P < 0.001). Seven percent (n = 980) developed DWRT-defined MI and 4.0% (n = 194) MMSE-defined MI during the follow-up. Only those with a short (≤ 5 h/day) sleep duration had a significantly increased risk of DWRT-defined MI (odds ratio = 1.53 (95% confidence interval; 1.21-1.93); P < 0.001) relative to normal sleepers (7 h/day). The association remained significant after excluding those with poor self-reported health. No associations were observed with MMSE-defined MI for both long and short sleep durations. CONCLUSIONS: This is the largest study to date addressing the association between extremes of sleep duration and memory decline. The observed adverse relationships provide support for an intervention study to examine the potential benefits of normalizing sleep duration in attenuating memory decline.