A meta-analysis of multiple myeloma risk regions in African and European ancestry populations identifies putatively functional loci

Rand, Kristin A.; Song, Chi; Dean, Eric; Serie, Daniel J.; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H.; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S.; Bock, Cathryn H.; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K.; V.Conti, David; Zimmerman, Todd; Hwang, Amie E.; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L.; Berndt, Sonja I.; Blot, William J.; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W. Ryan; Stevens, Victoria L.; Lieber, Michael R.; Goodman, Phyllis J.; Hennis, Anselm J.M.; Hsing, Ann W.; Mehta, Jayesh; Kittles, Rick A.; Kolb, Suzanne; Klein, Eric A.; Leske, Cristina; Murphy, Adam B.; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S.; Vij, Ravi; Rybicki, Benjamin A.; Stanford, Janet L.; Signorello, Lisa B.; Witte, John S.; Ambrosone, Christine B.; Bhatti, Parveen; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F.; Hu, Jennifer J.; Ziegler, Regina G.; Nyante, Sarah J.; Bandera, Elisa V.; Birmann, Brenda M.; Ingles, Sue A.; Press, Michael F.; Atanackovic, Djordje; Glenn, Martha J.; Cannon-Albright, Lisa A.; Jones, Brandt; Tricot, Guido; Martin, Thomas G.; Kumar, Shaji K.; Wolf, Jeffrey L.; Deming, Sandra L.; Rothman, Nathaniel; Brooks-Wilson, Angela R.; Rajkumar, S. Vincent; Kolonel, Laurence N.; Chanock, Stephen J.; Slager, Susan L.; Severson, Richard K.; Janakiraman, Nalini; Terebelo, Howard R.; Brown, Elizabeth E.; De Roos, Anneclaire J.; Mohrbacher, Ann F.; Colditz, Graham A.; Giles, Graham G.; Spinelli, John J.; Chiu, Brian C.; Munshi, Nikhil C.; Anderson, Kenneth C.; Levy, Joan; Zonder, Jeffrey A.; Orlowski, Robert Z.; Lonial, Sagar; Camp, Nicola J.; Vachon, Celine M.; Ziv, Elad; Stram, Daniel O.; Hazelett, Dennis J.; Haiman, Christopher A.; Cozen, Wendy

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A meta-analysis of multiple myeloma risk regions in African and European ancestry populations identifies putatively functional loci

Published Date:

Sep 01 2016

Source:

Cancer Epidemiol Biomarkers Prev. 25(12):1609-1618

Language:

English

[PDF-530.65 KB]

Details:

Personal Authors:

Rand, Kristin A. ; Song, Chi ; Dean, Eric ; Serie, Daniel J. ; Curtin, Karen ; ... More ▼

Keywords:

[+]

Pubmed ID:

27587788

Pubmed Central ID:

PMC5524541

Description:

Background

Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma (MM).

Methods

We performed association testing of common variation in eight regions in 1,264 MM patients and 1,479 controls of European ancestry (EA) and 1,305 MM patients and 7,078 controls of African ancestry (AA) 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 MM risk in AAs and EAs and the variant in 3p22.1 was associated in EAs only. In a combined AA-EA meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically signficantly associated with MM 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 tumor necrosis factor 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 MM 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 have consistent affects across populations and are likely to be functional.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

Supporting Files:

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	NIHMS814501-supplement-2.pdf	application/pdf
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