Dr. Danish Saleheen

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My research program is dedicated towards understanding genetic, blood-based and lifestyle factors that cause cardio-metabolic diseases; in particular my research focuses on (i) discovery of genetic risk factors predisposing to diseases like coronary heart disease, diabetes, fatty liver disease, CKD and stroke; (ii) understanding the relationship of biomarkers with the risk of non-communicable diseases; and (iii) understanding biological pathways by conducting deep phenotyping studies in humans who are homozygous null for loss of function mutations (i.e., "Human Knockouts"). In this respect, my group has enrolled > 65,000 participants in Pakistan on whom extensive information has been collected on lifestyle factors, genetic variants and circulating biomarkers; this bioresource is rapidly being expanded to 200,000 participants. Detailed phenotyping has been conducted on the participants already enrolled, including assay of GWAS chips, exome-chip and measurement of >200 biomarkers . More recently, whole-exome sequencing studies have been conducted in >22,500 participants as well. This population based resource in South Asia has positioned my group to investigate genetic risk factors in multi-ethnic populations through large scale meta-analyses. For instance, my group has co-led the discovery of 20 novel genes for coronary heart disease (CHD) and 6 novel genes for type-2 diabetes (T2D). My research program is particularly leveraging the high degree of consanguinity observed in Pakistanis to identify human knockouts. We are currently conducting a number of call-back studies on humans with such unique genotypes; for instance we have recently identified the world's first humans who have a complete deficiency of APOC3; these APOC3 human knockouts have already undergone a wide range of deep phenotyping studies to understand the function of APOC3 in human biology. 

 

Selected publications

1) Saleheen, D. et al. Human knockouts in a cohort with a high rate of consanguinity. Preprint at bioRxiv http://dx.doi.org/10.1101/031518 (2015)

2) Saleheen D, Scott R, Javad S, Zhao W, Rodrigues A, Picataggi A, Lukmanova D, Mucksavage ML, Luben R, Billheimer J, Kastelein JJ, Boekholdt SM, Khaw KT, Wareham N, Rader DJ. Lancet Diabetes Endocrinol. 2015 May 26. PMID: 26025389

3) Keenan T, Zhao W, Rasheed A, Ho WK, <<<29 authors>>, Saleheen D. J Am Coll Cardiol. 2016 2;67(4):407-16.  PMID: 26821629

4) Emdin CA, Khera AV, Natarajan P, Klarin D, Won HH, Peloso GM, Stitziel NO, Nomura A, Zekavat SM, Bick AG, Gupta N, Asselta R, Duga S, Merlini PA, Correa A, Kessler T, Wilson JG, Bown MJ, Hall AS, Braund PS, Samani NJ, Schunkert H, Marrugat J, Elosua R, McPherson R, Farrall M, Watkins H, Willer C, Abecasis GR, Felix JF, Vasan RS, Lander E, Rader DJ, Danesh J, Ardissino D, Gabriel S, Saleheen D, Kathiresan S; CHARGE–Heart Failure Consortium.; CARDIoGRAM Exome Consortium. J Am Coll Cardiol. 2016 Dec 27;68(25):2761-2772. PMID: 28007139

5) Saleheen D, Rader DJ, Voight BF. Disentangling the Causal Association of Plasma Lipid Traits and Type 2 Diabetes Using Human Genetics. AMA Cardiol. 2016 Sep 1;1(6):631-3. PMID: 27487162

6) Kooner JS*, Saleheen D* (joint first), Sim X, Sehmi J, Zhang W, Frossard P, et al . Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nat Genet. 2011 Aug 28;43(10):984-9 PMID: 21874001

7) Peden JF*, Hopewell JC*, Saleheen D* (joint first & corresponding author), et al. A genome-wide association study in Europeans and South Asians identifies five novel loci for coronary artery disease. Nat Genet. 2011 Mar 6;43(4):339-44 PMID: 21378988

8) Deloukas P*, Kanoni S*, Willenborg C*, Farrall M*, Assimes TL*, Thompson JR*, Ingelsson E*, Saleheen D (joint first), et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013 Jan;45(1):25-33.

9)  Nikpay M*, Goel A*, Won HH*, Hall LM*, Willenborg C*, Kanoni S*, Saleheen D* (joint first), et al.  A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet. 2015 Oct;47(10):1121-3

10) Nelson CP, Hamby SE, Saleheen D, et.al. Genetically determined height and coronary artery disease. N Engl J Med. 2015 Apr 23;372(17):1608-18. PMID: 25853659

11) Saleheen D, Zaidi M, Rasheed A, et.al. The Pakistan Risk of Myocardial Infarction Study: a resource for the study of genetic, lifestyle and other determinants of myocardial infarction in South Asia. Eur J Epidemiol. 2009;24(6):329-38. PMID: 19404752

12) Saleheen D, Zhao W, Rasheed A. Epidemiology and public health policy of tobacco use and cardiovascular disorders in low- and middle-income countries. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1811-9. PMID: 25035346

13) Saleheen D, Alexander M, Rasheed A, et.al. Association of the 9p21.3 Locus With Risk of First-Ever Myocardial Infarction in Pakistanis. Arterioscler Thromb Vasc Biol. 2010;30(7):1467-73. PMID: 20395598