A study published in the journal PLoS One (https://doi.org/10.1371/journal.pone.0217796 ) in 2019 presented results of a GWAS searching for loci impacting the risk of prolonged QRS in Hispanic/Latino people living in the U.S. QRS prolongation has been associated heart failure and cardiovascular mortality. The Manhattan plot below summarizes the results. The significance threshold for this study is shown as a horizontal line at -log₁0(p-value) ~7.5. The names of candidate genes at each associated locus are shown at the top of the corresponding SNP tower. How many loci containing at least one gene affecting prolonged QRS risk were identified? -log10(p) C 10- 2 0 SCN5A-SCN10A 2 3 CDKN1A HAND1 6 7 8 VTI1A 201 9 10 11 SYT1 MYOCD : ... 12 13 14 15 16 17 18 19 20 2122 XY -log10 (P-value) 30 25 20 15 10 5 0 B DLEC1- +ACAA1 OXSR1- MYD88- XYLB→ SLC22A13→ -LOC100128640 H SLC22A14→→→ H ACVR2B- T EXOG *SCN5A rs6801957

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A study published in the journal PLoS One
(https://doi.org/10.1371/journal.pone.0217796 ) in 2019 presented results of
a GWAS searching for loci impacting the risk of prolonged QRS in
Hispanic/Latino people living in the U.S. QRS prolongation has been associated
heart failure and cardiovascular mortality. The Manhattan plot below
summarizes the results. The significance threshold for this study is shown as a
horizontal line at -log₁0(p-value) ~7.5. The names of candidate genes at each
associated locus are shown at the top of the corresponding SNP tower. How
many loci containing at least one gene affecting prolonged QRS risk were
identified?
-log10(p)
C
10-
2
0
SCN5A-SCN10A
2
3
CDKN1A
HAND1
6
7
8
VTI1A
201
9
10
11
SYT1
MYOCD
:
...
12 13 14 15 16 17 18 19 20 2122 XY
Transcribed Image Text:A study published in the journal PLoS One (https://doi.org/10.1371/journal.pone.0217796 ) in 2019 presented results of a GWAS searching for loci impacting the risk of prolonged QRS in Hispanic/Latino people living in the U.S. QRS prolongation has been associated heart failure and cardiovascular mortality. The Manhattan plot below summarizes the results. The significance threshold for this study is shown as a horizontal line at -log₁0(p-value) ~7.5. The names of candidate genes at each associated locus are shown at the top of the corresponding SNP tower. How many loci containing at least one gene affecting prolonged QRS risk were identified? -log10(p) C 10- 2 0 SCN5A-SCN10A 2 3 CDKN1A HAND1 6 7 8 VTI1A 201 9 10 11 SYT1 MYOCD : ... 12 13 14 15 16 17 18 19 20 2122 XY
-log10 (P-value)
30
25
20
15
10
5
0
B
DLEC1-
+ACAA1
OXSR1-
MYD88-
XYLB→
SLC22A13→ -LOC100128640
H
SLC22A14→→→
H
ACVR2B-
T
EXOG
*SCN5A
rs6801957
<SCN10A
H
+SCN11A
WDR48→
+GORASP1
TTC21A-
+CSRNP1
As shown in the Manhattan plot in previous question, the authors have
identified a single best candidate gene for most loci identified in their study, but
identified two candidate genes for the locus on chromosome 3: SCN5A and
SCN10A. These are related genes that both encode cardiac sodium channels.
The regional association plot for this locus is shown above, with gene models in
this region shown below the plot. Based on the information shown here, why did
the authors nominate SCN5A and SCN10A as candidate genes, but not
SCN11A, another cardiac sodium channel gene adjacent to SCN10A? Limit your
answer to 1-2 sentences.
Transcribed Image Text:-log10 (P-value) 30 25 20 15 10 5 0 B DLEC1- +ACAA1 OXSR1- MYD88- XYLB→ SLC22A13→ -LOC100128640 H SLC22A14→→→ H ACVR2B- T EXOG *SCN5A rs6801957 <SCN10A H +SCN11A WDR48→ +GORASP1 TTC21A- +CSRNP1 As shown in the Manhattan plot in previous question, the authors have identified a single best candidate gene for most loci identified in their study, but identified two candidate genes for the locus on chromosome 3: SCN5A and SCN10A. These are related genes that both encode cardiac sodium channels. The regional association plot for this locus is shown above, with gene models in this region shown below the plot. Based on the information shown here, why did the authors nominate SCN5A and SCN10A as candidate genes, but not SCN11A, another cardiac sodium channel gene adjacent to SCN10A? Limit your answer to 1-2 sentences.
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