A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

BACKGROUND: Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. METHODS: We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. RESULTS: We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10-7) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. IMPACT: A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR.

Frequency and risk factors for pterygium in the Barbados Eye Study

OBJECTIVE: To describe the disrtibution and risk factors for pterygium in the predominantly black population of the Barbados Eye Study, which was based on a random sample for Barbadian-born citizens between the ages of 40 and 84 years. METHODS: The standardized protocol included ophtalmic and other measurements, automated perimetry, lens gradings, fundus photography, and a detailed interview. A 10 percent systematic sample of participants and those meeting specific criteria also received a comprehensive ophthalmologic evaluation. RESULTS: The Barbados Eye Study included 4709 participants, of whom 2978 were referred for an ophthalmologic evaluation and 2781 (93 percent) completed the examination. Cases of pterygium were found among 23.4 percent of 2617 black, 23.7 percent of 97 mixed (black and white), and 10.2 percent of 59 white participants examined. In addition to African ancestry, logistic regression analyses indicated a positive association between pterygium and age (odds ratio [OR], 1.01; 95 percent confidence interval [CI], 1.00-1.02), fewer years of education (OR, 1.43; 95 percent CI, 1.01-2.03), and an outdoor job location (OR, 1.87; 95 percent CI, 1.52-2.29). Having a darker skin complexion (OR, 0.66; 95 percent CI, 0.52-0.83), always using sunglasses outdoors (OR, 0.18; 95 percent CI, 0.06-0.59), and the use of prescription glasses (OR, 0.75; 95 percent CI, 0.60-0.93) were protective factors. CONCLUSIONS: Approximately one quarter of the black participants examined had pterygia, a frequency that was 2.5 to 3 times higher than among whites in the Barbados Eye Study and elsewhere. Pterygium was almost twice as frequent among persons who worked outdoors but only one fifth as likely among those who always used sun glasses outdoors. Educational interventions to modify these potential exposures may assist in preventing pterygium. (AU)

Incidence of open-angle glaucoma. The Barbados Eye studies

OBJECTIVE: To measure the 4-year risk of open-angle glaucoma (OAG) in a black population. DESIGN: Population-based cohort study with 4 years of follow up. SETTING: Simple random sample of residents of Barbados, West Indies, aged 40 years or older. PARTICIPANTS: A total of 3427 members of the cohort (85 percent of those eligible). MAIN OUTCOME MEASURE: Development of glaucoma visual field defects and optic disc damage, confirmed by automated perimetry, independent fundus photographic gradings, and standardized opthalmologic examinations. RESULTS: The 4-year risk of OAG in black participants was 2.2 percent (95 percent confidence interval, 1.7 percent-2.8 percent), based on 67 newly developed cases of OAG. Incidence rates increased from 1.2 percent at ages 40 to 49 years to 4.2 percent at ages of 70 years or more, tending to be higher in men than women (2.7 percent vs 1.9 percent). About half of the incident cases were undiagnosed previously, and the rest were receiving OAG treatment. Of the 67 new cases of OAG, 32 had intraocular pressure of 21 mm HG or less at baseline (1.2 percent incidence) and 35 had higher pressures (9 percent incidence). Risk was the highest among persons classified as having suspect OAG at baseline (26.1 percent), followed by those with ocular hypertension (4.9 percent and lowest in the remining population (0.8 percent). CONCLUSIONS: This longitudinal study provides new information on OAG risk, as well as the first incidence measurement in a black population. Although intraocular pressure increased risk, about half of the new cases had baseline pressures of 21 mm Hg or less. Results substantiate the high OAG risk in the population of African origin, especially in older adults; the relative role of intraocular pressure; and the considerable underdetecion of new disease after 4 years of follow-up. (AU)