A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Differences Between Essential Tremor Developing Parkinson&apos;s Disease and Essential Tremor

ÖZET Amaç: Esansiel tremor (ET) en yayg›n ekstrapiramidal hastal›kt›r ve baz› ET hastalar› sonradan Parkinson Hastal›¤› (PH) gelifltirebilirler. Ancak bugüne kadar kesin bir birliktelik tan›mlanmam›flt›r. Biz ET ve PH aras›ndaki iliflkiyi anlamak için, ET ile ET sonras› PH gelifltiren hastalar aras›ndaki farkl›l›klar› demografik ve klinik aç›dan araflt›rd›k. Yöntemler: Yüz k›rk dört ET ve 336 PH hastas› retrospektif olarak klinik kay›tla-r›ndan de¤erlendirildi ve yafl, cinsiyet, ET bafllama yafl›, ailede ET öyküsü, asimetrik veya simetrik tremor REM-uyku davran›fl bozuklu¤u (REM-SBD) öyküsü kaydedildi. Bulgular: Otuz üç PH öncesi ET&apos;si olan hasta önceki klinik kay›tlar›na dayanarak ETPD hastas› olarak de¤erlendirildi. ET&apos;den PH&apos;e dönme süresi ortalama 12±11.4 y›l idi (1-47). Gruplar aras›nda cinsiyet farkl›l›¤› yoktu. ET hastalar›nda ETPD hastalar› ile karfl›laflt›r›ld›¤›nda ortalama yafl, ET bafllama yafl›, asimetrik tremor ve REM-SBD öyküsü anlaml› olarak daha azd›. ET hastalar›nda ailede ET öyküsü ve bafl tremoru ETPD&apos;den daha fazla idi. Sonuç: Bizim sonuçlar›m›z asimetrik tremor, geç bafllang›çl› ET ve REM-SBD öyküsü olan ET hastalar›n›n sonradan PH gelifltirebilece¤ine dikkati çekmifltir. ABSTRACT Objective: Essential tremor (ET) is the most prevalent extrapyramidal disorder and some ET patients may later develop Parkinson&apos;s disease (PD). However, up to date, precise association was not determined. To understand the relationship between ET and PD, we investigated differences between patients with ET and ET developing PD (ETPD) in terms of demographic and clinical characteristics. Methods: One hundred forty-four patients with ET and 336 PD patients were retrospectively assessed from their clinical charts, and their current age, gender, onset age of ET, family history of ET, asymmetrical or symmetrical tremor and history of REM-Sleep Behavior Disorders (REM-SBD) were recorded. Results: Thirty-three patients who had ET prior to PD were evaluated as ETPD patients based on previous clinical records. The mean duration from ET to PD was 12±11.4 years (range: 1-47). There was no difference in gender between the groups. The mean age, the mean age at ET onset, asymmetrical tremor and REM-SBD history were significantly lower in ET patients compared to ETPD patients. The family history of ET and head tremor was more frequent in ET patients than in ETPD. Conclusions: Our results point out that some patients with ET, having asymmetrical tremor, late onset and REM-SBD history may develop PD

Reflexiones y aportes a la construcci?n de paz desde la Universidad del Tolima

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