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Introduction: We investigated cross-sectional relationships between arthritis or joint-related pain intensity and subjective cognitive decline in middle-aged and older adults. Methods: The sample consisted of 30,150 adults ⩾age 45 years with self-reported arthritis or joint conditions who completed key variables in the 2015 wave of the Behavioral Risk Factor Surveillance System. Results: Using weighted data, 94.2% of the sample reported experiencing joint pain in the last month (35.9% reported moderate pain and 30.6% reported severe pain) and 17.3% reported subjective cognitive decline. In logistic regression models, pain intensity was associated with significantly higher odds of reporting subjective cognitive decline, after controlling for age, race/ethnicity, sex, education, household income, cardiovascular health, mental health, and history of stroke. Those with moderate pain were two times as likely to report subjective cognitive decline and those with severe pain were more than three times as likely to report subjective cognitive decline relative to those without pain, adjusting for covariates. Conclusion: The results of this study highlight a significant relationship between pain intensity and subjective cognitive decline in middle-aged and older adults with arthritis or joint conditions typically associated with joint pain. Moderate and severe joint pain is significantly associated with higher risk of subjective cognitive decline, after controlling for personal and health characteristics. Future studies with more comprehensive assessments of pain and cognition are warranted to further elucidate these relationships and their underlying mechanisms.
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By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença/genética , Genoma Humano/genética , Polimorfismo de Nucleotídeo Único , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Fosfatases de Especificidade Dupla/genética , Jejum/sangue , Dosagem de Genes , Perfilação da Expressão Gênica , Heterogeneidade Genética , Estudo de Associação Genômica Ampla , Fator 1-alfa Nuclear de Hepatócito/genética , Humanos , Canal de Potássio KCNQ1/genética , Metanálise como Assunto , Fosfatases da Proteína Quinase Ativada por Mitógeno/genéticaRESUMO
Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
Assuntos
Índice de Massa Corporal , Peso Corporal/genética , Sistema Nervoso Central/fisiologia , Locos de Características Quantitativas/genética , Alelos , Antropometria , Estudos de Coortes , Dosagem de Genes , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Metanálise como Assunto , Obesidade/complicações , Obesidade/genética , Polimorfismo de Nucleotídeo Único/genética , Característica Quantitativa HerdávelRESUMO
Dissecting the genetic basis of disease risk requires measuring all forms of genetic variation, including SNPs and copy number variants (CNVs), and is enabled by accurate maps of their locations, frequencies and population-genetic properties. We designed a hybrid genotyping array (Affymetrix SNP 6.0) to simultaneously measure 906,600 SNPs and copy number at 1.8 million genomic locations. By characterizing 270 HapMap samples, we developed a map of human CNV (at 2-kb breakpoint resolution) informed by integer genotypes for 1,320 copy number polymorphisms (CNPs) that segregate at an allele frequency >1%. More than 80% of the sequence in previously reported CNV regions fell outside our estimated CNV boundaries, indicating that large (>100 kb) CNVs affect much less of the genome than initially reported. Approximately 80% of observed copy number differences between pairs of individuals were due to common CNPs with an allele frequency >5%, and more than 99% derived from inheritance rather than new mutation. Most common, diallelic CNPs were in strong linkage disequilibrium with SNPs, and most low-frequency CNVs segregated on specific SNP haplotypes.